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39058375_p48
|
39058375
|
sec[3]/p[14]
|
DISCUSSION
| 4.027344 |
biomedical
|
Study
|
[
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[
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Regarding the exclusion of participants in studies due to conditions that could influence cortisol levels, this factor can have important implications for the generalizability of the results and can introduce potential biases into the conclusions. By restricting participation on the basis of cortisol-related factors, such as medical conditions or the use of medications that affect hormone regulation, there is a risk of limiting the representativeness of the sample. On the other hand, selective exclusion of participants can result in a more homogeneous sample, underestimating or overestimating the effects of cortisol. In this way, researchers should be aware of all the conditions that can modulate cortisol, reducing the risk of confounding bias.
|
[
"Jackson Gois Teixeira",
"Lucas Tomaz Benigno Lima",
"Elaine Carvalho Cunha",
"Flavia Oliveira de Almeida Marques da Cruz",
"Karen Karoline Gouveia Carneiro",
"Laiane Medeiros Ribeiro",
"Guilherme da Costa Brasil",
"Jackson Gois Teixeira",
"Lucas Tomaz Benigno Lima",
"Elaine Carvalho Cunha",
"Flavia Oliveira de Almeida Marques da Cruz",
"Karen Karoline Gouveia Carneiro",
"Laiane Medeiros Ribeiro",
"Guilherme da Costa Brasil"
] |
https://doi.org/10.1590/1980-220X-REEUSP-2023-0279en
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999999 |
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|
39058375
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|
DISCUSSION
| 3.816406 |
biomedical
|
Study
|
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As for the limitations of the studies, it is important to highlight the blinding bias of the participants and evaluators and the lack of a validated performance evaluation tool suitable for the scenarios, making it impossible to generalize the results and the small sample size as it does not provide the necessary statistical power. Some studies had participants with different levels of experience, training and specialty in their sample, and the sample population was chosen for convenience or included on a voluntary basis, which can have a negative impact on the level of evidence in the studies. Furthermore, most of the studies did not address the participants’ previous experience with the simulation.
|
[
"Jackson Gois Teixeira",
"Lucas Tomaz Benigno Lima",
"Elaine Carvalho Cunha",
"Flavia Oliveira de Almeida Marques da Cruz",
"Karen Karoline Gouveia Carneiro",
"Laiane Medeiros Ribeiro",
"Guilherme da Costa Brasil",
"Jackson Gois Teixeira",
"Lucas Tomaz Benigno Lima",
"Elaine Carvalho Cunha",
"Flavia Oliveira de Almeida Marques da Cruz",
"Karen Karoline Gouveia Carneiro",
"Laiane Medeiros Ribeiro",
"Guilherme da Costa Brasil"
] |
https://doi.org/10.1590/1980-220X-REEUSP-2023-0279en
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
39058375_p50
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39058375
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sec[3]/p[16]
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DISCUSSION
| 3.265625 |
biomedical
|
Review
|
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In relation to the limitations inherent to this review, we would highlight the lack of a meta-analysis due to the heterogeneity of the studies included in relation to method, sample design and statistical analysis. There were also challenges related to access to data in some studies and, unfortunately, when trying to contact the author responsible for the article, we were unsuccessful. This difficulty may have resulted in the possible loss of relevant information that could have contributed to the inclusion and understanding of this review.
|
[
"Jackson Gois Teixeira",
"Lucas Tomaz Benigno Lima",
"Elaine Carvalho Cunha",
"Flavia Oliveira de Almeida Marques da Cruz",
"Karen Karoline Gouveia Carneiro",
"Laiane Medeiros Ribeiro",
"Guilherme da Costa Brasil",
"Jackson Gois Teixeira",
"Lucas Tomaz Benigno Lima",
"Elaine Carvalho Cunha",
"Flavia Oliveira de Almeida Marques da Cruz",
"Karen Karoline Gouveia Carneiro",
"Laiane Medeiros Ribeiro",
"Guilherme da Costa Brasil"
] |
https://doi.org/10.1590/1980-220X-REEUSP-2023-0279en
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
39058375_p51
|
39058375
|
sec[3]/p[17]
|
DISCUSSION
| 4.019531 |
biomedical
|
Review
|
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The review presented here has allowed us to expand our knowledge of the association between cortisol levels and performance in clinical simulation, highlighting the complexity of the interactions between the endocrine system and performance in simulated environments. The results could be essential for teachers and professionals working with clinical simulation, the studies should take into account the participant’s stress level and the conditions that modulate stress, since cortisol regulation can play a crucial role in the participant’s adaptation and performance. Furthermore, they need to be careful when designing a clinical scenario, knowing the factors that affect performance can contribute to improving clinical practice and enhancing the quality of health care. In addition, stress management must be taken into account so that the simulation is not a trauma, but a form of learning for the student.
|
[
"Jackson Gois Teixeira",
"Lucas Tomaz Benigno Lima",
"Elaine Carvalho Cunha",
"Flavia Oliveira de Almeida Marques da Cruz",
"Karen Karoline Gouveia Carneiro",
"Laiane Medeiros Ribeiro",
"Guilherme da Costa Brasil",
"Jackson Gois Teixeira",
"Lucas Tomaz Benigno Lima",
"Elaine Carvalho Cunha",
"Flavia Oliveira de Almeida Marques da Cruz",
"Karen Karoline Gouveia Carneiro",
"Laiane Medeiros Ribeiro",
"Guilherme da Costa Brasil"
] |
https://doi.org/10.1590/1980-220X-REEUSP-2023-0279en
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
39058375_p52
|
39058375
|
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|
CONCLUSION
| 3.933594 |
biomedical
|
Review
|
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This is the first systematic review on the impact of cortisol on performance in simulations, to the best of our knowledge. As cortisol levels change, participants’ performance changes, either in a detrimental or beneficial way. However, in other studies there was no correlation between stress and performance, which may not have been due to methodological issues. It is clear that there is a lack of robust scientific evidence in this area, highlighting the urgent need for more careful and well-designed research. With regard to the research gap, it is not known to what extent stress can be beneficial or detrimental to performance and whether this variation is changeable according to the level of difficulty of the scenario or stressors in the simulation scenario.
|
[
"Jackson Gois Teixeira",
"Lucas Tomaz Benigno Lima",
"Elaine Carvalho Cunha",
"Flavia Oliveira de Almeida Marques da Cruz",
"Karen Karoline Gouveia Carneiro",
"Laiane Medeiros Ribeiro",
"Guilherme da Costa Brasil",
"Jackson Gois Teixeira",
"Lucas Tomaz Benigno Lima",
"Elaine Carvalho Cunha",
"Flavia Oliveira de Almeida Marques da Cruz",
"Karen Karoline Gouveia Carneiro",
"Laiane Medeiros Ribeiro",
"Guilherme da Costa Brasil"
] |
https://doi.org/10.1590/1980-220X-REEUSP-2023-0279en
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
39058375_p53
|
39058375
|
sec[4]/p[1]
|
CONCLUSION
| 3.910156 |
biomedical
|
Other
|
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With regard to future studies, it is suggested that well-designed randomized clinical trials be carried out to reduce the risk of bias and that they cover a wide range of fidelities, from low to high fidelity trials that assess causality between exposure and outcome, significantly increasing the sample size and having a distinct population in their sample.
|
[
"Jackson Gois Teixeira",
"Lucas Tomaz Benigno Lima",
"Elaine Carvalho Cunha",
"Flavia Oliveira de Almeida Marques da Cruz",
"Karen Karoline Gouveia Carneiro",
"Laiane Medeiros Ribeiro",
"Guilherme da Costa Brasil",
"Jackson Gois Teixeira",
"Lucas Tomaz Benigno Lima",
"Elaine Carvalho Cunha",
"Flavia Oliveira de Almeida Marques da Cruz",
"Karen Karoline Gouveia Carneiro",
"Laiane Medeiros Ribeiro",
"Guilherme da Costa Brasil"
] |
https://doi.org/10.1590/1980-220X-REEUSP-2023-0279en
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277703_p0
|
PMC11277703
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|
1. Introduction
| 2.302734 |
biomedical
|
Other
|
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[
0.00487518310546875,
0.9267578125,
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Skin cancer is one of the most common types of cancer worldwide, with an increasing incidence over recent decades. It poses significant public health challenges due to its high prevalence and potential for severe outcomes . According to recent statistics, millions of new cases are diagnosed annually, highlighting the urgent need for effective prevention and treatment strategies .
|
[
"Georgia Vairaktari",
"Alexander Schramm",
"Efstathia Vairaktari",
"Spyridoula Derka",
"Andreas Sakkas",
"Nikolaos Lefantzis",
"Stavroula Diamantopoulou",
"Antonis Vylliotis",
"Andreas Lazaris",
"Marcel Ebeling",
"Stavros Vassiliou"
] |
https://doi.org/10.3390/jpm14070729
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11277703_p1
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|
1. Introduction
| 3.972656 |
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|
Study
|
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Among the various forms of skin cancer, cutaneous squamous cell carcinoma (cSCC) is particularly noteworthy for its aggressive nature and potential to metastasize. cSCC arises from the keratinocytes of the epidermis and is influenced by factors such as ultraviolet radiation exposure, immunosuppression, and genetic predispositions . Understanding the molecular mechanisms driving cSCC progression is crucial for developing targeted therapies .
|
[
"Georgia Vairaktari",
"Alexander Schramm",
"Efstathia Vairaktari",
"Spyridoula Derka",
"Andreas Sakkas",
"Nikolaos Lefantzis",
"Stavroula Diamantopoulou",
"Antonis Vylliotis",
"Andreas Lazaris",
"Marcel Ebeling",
"Stavros Vassiliou"
] |
https://doi.org/10.3390/jpm14070729
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
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|
1. Introduction
| 4.066406 |
biomedical
|
Study
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Recent studies have highlighted the roles of various oncogenes in skin cancer, including NOTCH1 and FGFR2. While NOTCH1 has been extensively studied, the role of FGFR2 in cSCC remains less understood . This study aims to evaluate the activation of NOTCH1 and FGFR2 oncogenes in inducing skin cancer in FVB/N mice through a stepwise chemical process, providing new insights into their involvement in cSCC development.
|
[
"Georgia Vairaktari",
"Alexander Schramm",
"Efstathia Vairaktari",
"Spyridoula Derka",
"Andreas Sakkas",
"Nikolaos Lefantzis",
"Stavroula Diamantopoulou",
"Antonis Vylliotis",
"Andreas Lazaris",
"Marcel Ebeling",
"Stavros Vassiliou"
] |
https://doi.org/10.3390/jpm14070729
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277703_p3
|
PMC11277703
|
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|
1. Introduction
| 4.5625 |
biomedical
|
Study
|
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Notch proteins are transmembrane receptors that respond to transmembrane ligands and play a crucial role in various developmental and cellular processes, including carcinogenesis. Upon ligand engagement, Notch undergoes a bipartite proteolytic cleavage cascade, resulting in the release of the Notch Intracellular Domain (NICD) for nuclear translocation. NICD acts as a transcriptional modulator within the nucleus, regulating gene expression . Notch1 is a crucial component of the Notch signaling pathway and has been linked to various types of cancer, including T-acute lymphoblastic leukemia. When hyperactivated or hyperstabilized, Notch1 acts as a proto-oncogene, promoting the initiation and progression of carcinogenesis . However, in skin keratinocytes, Notch1 has been attributed a paradoxical ‘tumor suppressor’ role , although the precise mechanism underlying this unique function remains controversial.
|
[
"Georgia Vairaktari",
"Alexander Schramm",
"Efstathia Vairaktari",
"Spyridoula Derka",
"Andreas Sakkas",
"Nikolaos Lefantzis",
"Stavroula Diamantopoulou",
"Antonis Vylliotis",
"Andreas Lazaris",
"Marcel Ebeling",
"Stavros Vassiliou"
] |
https://doi.org/10.3390/jpm14070729
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11277703_p4
|
PMC11277703
|
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|
1. Introduction
| 4.253906 |
biomedical
|
Study
|
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The removal of Notch from the epidermal layer has been linked to the development of cutaneous neoplasms . This has led to the identification of Notch1 as a potential tumor suppressor in epidermal biology . However, the exact mechanisms that govern the tumor suppressive role of Notch1 in this context are not yet fully understood. It is also unclear whether other Notch paralogues, such as Notch2 and 3, compensate for its absence in the skin. Notch1’s tumor suppressor activity is proposed to stem from its unique ability to counteract keratinocyte proliferation through one or more cell-autonomous signaling mechanisms. While these insights primarily originate from studies on the precancerous hyperplastic epidermis of Notch-deficient animals , early changes following Notch loss have not been comprehensively explored.
|
[
"Georgia Vairaktari",
"Alexander Schramm",
"Efstathia Vairaktari",
"Spyridoula Derka",
"Andreas Sakkas",
"Nikolaos Lefantzis",
"Stavroula Diamantopoulou",
"Antonis Vylliotis",
"Andreas Lazaris",
"Marcel Ebeling",
"Stavros Vassiliou"
] |
https://doi.org/10.3390/jpm14070729
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11277703_p5
|
PMC11277703
|
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|
1. Introduction
| 2.837891 |
biomedical
|
Study
|
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[
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In vitro studies with isolated keratinocytes were used to draw conclusions . However, these studies overlooked the complexities of the skin microenvironment and the contributions of other skin components to carcinogenesis.
|
[
"Georgia Vairaktari",
"Alexander Schramm",
"Efstathia Vairaktari",
"Spyridoula Derka",
"Andreas Sakkas",
"Nikolaos Lefantzis",
"Stavroula Diamantopoulou",
"Antonis Vylliotis",
"Andreas Lazaris",
"Marcel Ebeling",
"Stavros Vassiliou"
] |
https://doi.org/10.3390/jpm14070729
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999999 |
PMC11277703_p6
|
PMC11277703
|
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|
1. Introduction
| 4.261719 |
biomedical
|
Study
|
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In vivo studies have shown that the inhibition of Notch signaling during embryonic development leads to epidermal hypoplasia and reduced proliferative capacity in keratinocytes. This suggests that reactive or secondary hyperplasia may underlie the subsequently observed late-stage epidermal hyperproliferation in adult skin lacking Notch activity . The molecular alterations described so far may indicate secondary cascades that occur after epidermal hyperplasia in mice that do not have functional Notch signaling.
|
[
"Georgia Vairaktari",
"Alexander Schramm",
"Efstathia Vairaktari",
"Spyridoula Derka",
"Andreas Sakkas",
"Nikolaos Lefantzis",
"Stavroula Diamantopoulou",
"Antonis Vylliotis",
"Andreas Lazaris",
"Marcel Ebeling",
"Stavros Vassiliou"
] |
https://doi.org/10.3390/jpm14070729
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
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|
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|
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|
1. Introduction
| 4.53125 |
biomedical
|
Study
|
[
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[
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The Fibroblast Growth Factor Receptor (FGFR) family is a subset of human Receptor Tyrosine Kinases (RTKs), consisting of four extensively conserved transmembrane receptors (FGFR1-4) and one FGF receptor characterized by the absence of an intracellular domain (FGFR5). Although FGFRs are mainly located at the cellular periphery, they can also be found inside organelles such as the nucleus and mitochondria . Cell membrane-bound FGFRs typically have a ligand-binding extracellular domain with three immunoglobulin-like (Ig-like) domains, a transmembrane helical segment, and a cytoplasmic domain containing a catalytically active tyrosine kinase module. Alternative splicing events, particularly in the third Ig-like domain, create a range of FGFR isoforms with different ligand affinities and specificities .
|
[
"Georgia Vairaktari",
"Alexander Schramm",
"Efstathia Vairaktari",
"Spyridoula Derka",
"Andreas Sakkas",
"Nikolaos Lefantzis",
"Stavroula Diamantopoulou",
"Antonis Vylliotis",
"Andreas Lazaris",
"Marcel Ebeling",
"Stavros Vassiliou"
] |
https://doi.org/10.3390/jpm14070729
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11277703_p8
|
PMC11277703
|
sec[0]/p[8]
|
1. Introduction
| 4.480469 |
biomedical
|
Study
|
[
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[
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Fibroblast Growth Factors (FGFs) and their cognate receptors coordinate various physiological processes, including cellular proliferation, differentiation, and motility . Upon phosphorylation of FGFR, several intracellular signaling cascades are activated, including the RAS–RAF–mitogen-activated protein kinase (MAPK)–extracellular regulated kinase (ERK), PI3K/AKT, Stat3, and NFKB pathways, all of which have been linked to skin carcinogenesis . Elevated levels of FGFR have been found in various types of cancer, including prostate, breast, and lung cancers. However, its role in skin cancer remains relatively unexplored . Previous studies have highlighted the importance of FGFR2 gene amplification, aberrant activation, or single-nucleotide polymorphisms in driving oncogenic progression . In our previous research involving SKH-1 mice, exposure to UVB radiation resulted in increased FGFR2 phosphorylation in the skin. Preemptive treatment with AZD4547, a selective FGFR inhibitor, significantly reduced UVB-induced FGFR2 activation, thereby reducing UVB-triggered epidermal hyperplasia and hyperproliferation, which are key early events in UVB-induced carcinogenesis . However, the potential therapeutic use of FGFRs in modulating the promotion and progression of cutaneous squamous cell carcinoma (cSCC) has yet to be explored.
|
[
"Georgia Vairaktari",
"Alexander Schramm",
"Efstathia Vairaktari",
"Spyridoula Derka",
"Andreas Sakkas",
"Nikolaos Lefantzis",
"Stavroula Diamantopoulou",
"Antonis Vylliotis",
"Andreas Lazaris",
"Marcel Ebeling",
"Stavros Vassiliou"
] |
https://doi.org/10.3390/jpm14070729
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
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|
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|
1. Introduction
| 4.734375 |
biomedical
|
Study
|
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Several studies have shown that UVB radiation can activate the mTOR pathway in skin keratinocytes . The mTOR pathway is a crucial serine/threonine kinase that plays various roles, including cellular stress responses, growth factor signaling, nutrient sensing, and stress signal transduction . Photocarcinogenesis involves the inhibition of apoptosis and the stimulation of proliferation through mTOR, which is often enhanced by upstream signals such as Ras or phosphoinositide 3-kinase (PI3K). This leads to increased proliferation and reduced susceptibility to apoptotic stimuli . The mTOR pathway consists of rapamycin-sensitive mTORC1 and rapamycin-resistant mTORC2 complexes. In epidermal tumors such as cutaneous squamous cell carcinoma (cSCC) and precancerous actinic keratoses (AKs), the mTOR pathway exhibits elevated phosphorylation levels of mTOR, AKT, and their downstream effectors in comparison to normal skin . UVB-induced phosphorylation events targeting 4EBP1, S6K, and AKT underscore the pivotal role of the mTOR pathway in fostering tumorigenesis. FGFR2 transmits regulatory signals to downstream effectors by modulating the mTOR pathway. In mouse embryonic fibroblasts, mTOR activation suppresses autophagy facilitated by FGF receptor substrate 2α (FRS2α) and PI3K/AKT, highlighting the essential role of mTOR activation in mediating FGF’s autophagy-suppressive effects .
|
[
"Georgia Vairaktari",
"Alexander Schramm",
"Efstathia Vairaktari",
"Spyridoula Derka",
"Andreas Sakkas",
"Nikolaos Lefantzis",
"Stavroula Diamantopoulou",
"Antonis Vylliotis",
"Andreas Lazaris",
"Marcel Ebeling",
"Stavros Vassiliou"
] |
https://doi.org/10.3390/jpm14070729
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277703_p10
|
PMC11277703
|
sec[0]/p[10]
|
1. Introduction
| 4.109375 |
biomedical
|
Study
|
[
0.99951171875,
0.00028395652770996094,
0.00018775463104248047
] |
[
0.99951171875,
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0.00006383657455444336
] |
The primary objective of this investigation was to assess the expression patterns of the NOTCH1 and FGFR2 genes and to explore potential correlations between them across successive histological stages of cutaneous squamous cell carcinoma development in an experimental animal model of skin carcinogenesis. A secondary objective was to assess the utility of our two-stage carcinogenesis protocol in elucidating the involvement of additional genes in skin oncogenesis. Notably, this study represents the first and novel investigation of these objectives in a mouse model.
|
[
"Georgia Vairaktari",
"Alexander Schramm",
"Efstathia Vairaktari",
"Spyridoula Derka",
"Andreas Sakkas",
"Nikolaos Lefantzis",
"Stavroula Diamantopoulou",
"Antonis Vylliotis",
"Andreas Lazaris",
"Marcel Ebeling",
"Stavros Vassiliou"
] |
https://doi.org/10.3390/jpm14070729
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11277703_p11
|
PMC11277703
|
sec[1]/sec[0]/p[0]
|
2.1. Animals
| 4.023438 |
biomedical
|
Study
|
[
0.99951171875,
0.00018334388732910156,
0.00039649009704589844
] |
[
0.9990234375,
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Forty female FVB/N mice, aged four weeks and weighing approximately 100 g each, were obtained from the Hellenic Pasteur Institute in Athens, Greece. The FVB strain is an inbred laboratory mouse lineage named for its susceptibility to Friend leukemia virus B. It is highly favored in transgenic research due to its large litter sizes and oocytes with prominent pronuclei. Notably, this distinctive phenotype is only present in oocytes and not in sperm. The FVB/N strain was chosen for its susceptibility to skin tumors, as documented in prior studies, making it suitable for the current investigation. Age-matched female mice were selected due to the proclivity for male aggression and the impracticality of group housing male cohorts .
|
[
"Georgia Vairaktari",
"Alexander Schramm",
"Efstathia Vairaktari",
"Spyridoula Derka",
"Andreas Sakkas",
"Nikolaos Lefantzis",
"Stavroula Diamantopoulou",
"Antonis Vylliotis",
"Andreas Lazaris",
"Marcel Ebeling",
"Stavros Vassiliou"
] |
https://doi.org/10.3390/jpm14070729
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277703_p12
|
PMC11277703
|
sec[1]/sec[0]/p[1]
|
2.1. Animals
| 3.847656 |
biomedical
|
Study
|
[
0.9990234375,
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[
0.99560546875,
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The mice were handled in accordance with the ethical standards outlined in the Guide for the Care and Use of Laboratory Animals: Eighth Edition After a two-week acclimatization period in our facility, during which they were provided with rodent chow and ad libitum access to tap water, the animals were randomly assigned to four groups: a control group (group C: n = 8) and two experimental groups for carcinogen treatment (group A: n = 16, group B: n = 16). Rigorous randomization procedures were implemented to ensure unbiased group allocation, and the study design meticulously adhered to the ARRIVE guidelines, emphasizing transparency and reproducibility in research.
|
[
"Georgia Vairaktari",
"Alexander Schramm",
"Efstathia Vairaktari",
"Spyridoula Derka",
"Andreas Sakkas",
"Nikolaos Lefantzis",
"Stavroula Diamantopoulou",
"Antonis Vylliotis",
"Andreas Lazaris",
"Marcel Ebeling",
"Stavros Vassiliou"
] |
https://doi.org/10.3390/jpm14070729
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277703_p13
|
PMC11277703
|
sec[1]/sec[0]/p[2]
|
2.1. Animals
| 3.0625 |
biomedical
|
Study
|
[
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0.0014142990112304688
] |
[
0.8857421875,
0.11163330078125,
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0.0008001327514648438
] |
For optimal housing conditions, four mice were placed in each cage, which was lined with corn cob bedding and subjected to a 12 h light/dark cycle. Each animal was uniquely identified through an ear tattoo code, ensuring traceability throughout the study period. This approach to experimental design, housing, and identification is crucial in maintaining the welfare of the animals and upholding the scientific rigor of the investigation.
|
[
"Georgia Vairaktari",
"Alexander Schramm",
"Efstathia Vairaktari",
"Spyridoula Derka",
"Andreas Sakkas",
"Nikolaos Lefantzis",
"Stavroula Diamantopoulou",
"Antonis Vylliotis",
"Andreas Lazaris",
"Marcel Ebeling",
"Stavros Vassiliou"
] |
https://doi.org/10.3390/jpm14070729
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11277703_p14
|
PMC11277703
|
sec[1]/sec[1]/p[0]
|
2.2. Two-Stage Carcinogenesis Protocol
| 3.142578 |
biomedical
|
Study
|
[
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] |
[
0.9951171875,
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Forty female FVB/N mice, aged four weeks, underwent dorsal surface shaving using electric clippers to determine their hair cycle phase. After assessment, all mice were found to be in the telogen phase and were included in the study according to the criteria established by Mardaryev .
|
[
"Georgia Vairaktari",
"Alexander Schramm",
"Efstathia Vairaktari",
"Spyridoula Derka",
"Andreas Sakkas",
"Nikolaos Lefantzis",
"Stavroula Diamantopoulou",
"Antonis Vylliotis",
"Andreas Lazaris",
"Marcel Ebeling",
"Stavros Vassiliou"
] |
https://doi.org/10.3390/jpm14070729
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11277703_p15
|
PMC11277703
|
sec[1]/sec[1]/p[1]
|
2.2. Two-Stage Carcinogenesis Protocol
| 4.101563 |
biomedical
|
Study
|
[
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[
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One week after hair removal, the animals in groups A (n = 16) and B (n = 16) were anesthetized with ether and topically treated on the dorsal skin with 97.4 nmol of the initiator 7,12-dimethylbenz[a]anthracene (DMBA) using a #4 camel’s hairbrush (Sigma, St. Louis, MO, USA). A repeated application regimen involving 32.4 nmol of the tumor promoter 12-O-tetradecanoyl phorbol-13-acetate (TPA) was administered twice within a four-day interval per week . The TPA treatment duration spanned 13 weeks for group A and 20 weeks for group B, aligning with the regimen proposed by Abel et al. . The control group, denoted as group C (n = 8), received no applications.
|
[
"Georgia Vairaktari",
"Alexander Schramm",
"Efstathia Vairaktari",
"Spyridoula Derka",
"Andreas Sakkas",
"Nikolaos Lefantzis",
"Stavroula Diamantopoulou",
"Antonis Vylliotis",
"Andreas Lazaris",
"Marcel Ebeling",
"Stavros Vassiliou"
] |
https://doi.org/10.3390/jpm14070729
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277703_p16
|
PMC11277703
|
sec[1]/sec[1]/p[2]
|
2.2. Two-Stage Carcinogenesis Protocol
| 4.003906 |
biomedical
|
Study
|
[
0.9990234375,
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[
0.9970703125,
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] |
Weekly examinations were conducted to observe the lesions and tumor growth on the animal skin. Dermatological assessments were performed by two experienced dermatologists in the field of skin cancer, following the methodology outlined by Quintanilla et al. , which included observation, palpation, and dermatoscopy. Any palpable mass exceeding 1 mm in size that persisted for more than 2 weeks was meticulously recorded, following the criteria established by DiGiovanni .
|
[
"Georgia Vairaktari",
"Alexander Schramm",
"Efstathia Vairaktari",
"Spyridoula Derka",
"Andreas Sakkas",
"Nikolaos Lefantzis",
"Stavroula Diamantopoulou",
"Antonis Vylliotis",
"Andreas Lazaris",
"Marcel Ebeling",
"Stavros Vassiliou"
] |
https://doi.org/10.3390/jpm14070729
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11277703_p17
|
PMC11277703
|
sec[1]/sec[1]/p[3]
|
2.2. Two-Stage Carcinogenesis Protocol
| 3.851563 |
biomedical
|
Study
|
[
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[
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] |
Finally, all animals were euthanized via isoflurane overdose. Visible lesions on the treated skin were excised either fourteen weeks (group A) or twenty-one weeks (group B) after the application of the carcinogen. The tumor sizes were approximately 1 cm in most cases. Furthermore, at fourteen weeks, the control group C was euthanized, and a tissue sample was excised from their dorsal skin. All samples collected from groups A, B, and C were assigned numbers and evaluated impartially.
|
[
"Georgia Vairaktari",
"Alexander Schramm",
"Efstathia Vairaktari",
"Spyridoula Derka",
"Andreas Sakkas",
"Nikolaos Lefantzis",
"Stavroula Diamantopoulou",
"Antonis Vylliotis",
"Andreas Lazaris",
"Marcel Ebeling",
"Stavros Vassiliou"
] |
https://doi.org/10.3390/jpm14070729
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277703_p18
|
PMC11277703
|
sec[1]/sec[2]/p[0]
|
2.3. Histopathological Analysis
| 4.058594 |
biomedical
|
Study
|
[
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[
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A cohort of 459 biopsy samples were fixed in a 10% neutralized formaldehyde solution and embedded in paraffin. Three 4 mm sections were then prepared from each specimen and affixed to Super Frost Plus-coated glass slides (Menzel and Co., Braunschweig, Germany). For the standard histological analysis, one section was stained with hematoxylin and eosin, while the other two sections were used for the immunohistochemical detection of NOTCH1 and FGFR2 gene products.
|
[
"Georgia Vairaktari",
"Alexander Schramm",
"Efstathia Vairaktari",
"Spyridoula Derka",
"Andreas Sakkas",
"Nikolaos Lefantzis",
"Stavroula Diamantopoulou",
"Antonis Vylliotis",
"Andreas Lazaris",
"Marcel Ebeling",
"Stavros Vassiliou"
] |
https://doi.org/10.3390/jpm14070729
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11277703_p19
|
PMC11277703
|
sec[1]/sec[2]/p[1]
|
2.3. Histopathological Analysis
| 4.140625 |
biomedical
|
Study
|
[
0.9990234375,
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[
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] |
The histological examination involved a thorough analysis of the entire section under light microscopy, enabling the classification of tissue profiles into distinct categories. The categories assessed in this study included normal, hyperkeratosis, hyperplasia, dysplasia (low grade and high grade), papillomas, in situ carcinoma, well-differentiated squamous cell carcinoma, and poorly differentiated squamous cell carcinoma (refer to Table 1 for additional information). It is important to note that each sample was meticulously evaluated, with all distinct lesions assessed and categorized independently. This rigorous histopathological approach ensures a detailed and nuanced understanding of the varied tissue alterations present in the biopsy samples. For benign tumors, we defined criteria such as well-demarcated borders, the absence of invasion into surrounding tissues, and resemblance to a normal tissue architecture under microscopic examination. Malignant tumors were classified based on criteria including cellular pleomorphism, invasion into adjacent tissues, and the presence of mitotic figures. Precancerous lesions were identified by cellular atypia, dysplastic changes, and early signs of abnormal growth patterns without invasion. These criteria were applied consistently across all samples by a trained histopathologist to ensure robust classification.
|
[
"Georgia Vairaktari",
"Alexander Schramm",
"Efstathia Vairaktari",
"Spyridoula Derka",
"Andreas Sakkas",
"Nikolaos Lefantzis",
"Stavroula Diamantopoulou",
"Antonis Vylliotis",
"Andreas Lazaris",
"Marcel Ebeling",
"Stavros Vassiliou"
] |
https://doi.org/10.3390/jpm14070729
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11277703_p20
|
PMC11277703
|
sec[1]/sec[3]/p[0]
|
2.4. Immunohistochemical Analysis
| 3.898438 |
biomedical
|
Study
|
[
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[
0.9921875,
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The tissue sections were incubated with antibodies targeting NOTCH1 and FGFR2. The FGFR2 and NOTCH1 polyclonal antibodies are recommended for detecting FGFR2 and NOTCH1 of human and mouse origin using various techniques, including Western blot (WB), immunohistochemistry (Paraffin) (IHC (P)), immunocytochemistry (ICC/IF), and flow cytometry (Flow), at concentrations of 0.5 and 0.2 mg/mL, respectively. The antibodies used in this study were sourced from Thermo Fisher Scientific.
|
[
"Georgia Vairaktari",
"Alexander Schramm",
"Efstathia Vairaktari",
"Spyridoula Derka",
"Andreas Sakkas",
"Nikolaos Lefantzis",
"Stavroula Diamantopoulou",
"Antonis Vylliotis",
"Andreas Lazaris",
"Marcel Ebeling",
"Stavros Vassiliou"
] |
https://doi.org/10.3390/jpm14070729
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11277703_p21
|
PMC11277703
|
sec[1]/sec[3]/p[1]
|
2.4. Immunohistochemical Analysis
| 4.105469 |
biomedical
|
Study
|
[
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[
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The incubation process followed the standard immunohistochemical methodology, as outlined by Derka et al. . Positive controls for NOTCH1 and FGFR2 included a pancreas with robust NOTCH1 expression and a liver with strong FGFR2 expression. These tissues were selected based on their well-established expression profiles of NOTCH1 and FGFR2, ensuring that our antibodies were correctly detecting the target proteins in our experimental conditions. In parallel, negative controls were processed alongside the experimental samples, where phosphate-buffered saline (PBS) was substituted for the primary antibody. This step was crucial in confirming the specificity of our immunohistochemical staining, ensuring that any observed staining was attributable solely to the presence of NOTCH1 and FGFR2 proteins and not to non-specific interactions or background staining.
|
[
"Georgia Vairaktari",
"Alexander Schramm",
"Efstathia Vairaktari",
"Spyridoula Derka",
"Andreas Sakkas",
"Nikolaos Lefantzis",
"Stavroula Diamantopoulou",
"Antonis Vylliotis",
"Andreas Lazaris",
"Marcel Ebeling",
"Stavros Vassiliou"
] |
https://doi.org/10.3390/jpm14070729
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11277703_p22
|
PMC11277703
|
sec[1]/sec[3]/p[2]
|
2.4. Immunohistochemical Analysis
| 3.449219 |
biomedical
|
Study
|
[
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[
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To ensure an unbiased evaluation, two investigators who were blinded to the experimental conditions independently reviewed all samples. This meticulous approach to immunohistochemical analysis, which incorporated positive and negative controls, reinforces the reliability and validity of the study’s findings.
|
[
"Georgia Vairaktari",
"Alexander Schramm",
"Efstathia Vairaktari",
"Spyridoula Derka",
"Andreas Sakkas",
"Nikolaos Lefantzis",
"Stavroula Diamantopoulou",
"Antonis Vylliotis",
"Andreas Lazaris",
"Marcel Ebeling",
"Stavros Vassiliou"
] |
https://doi.org/10.3390/jpm14070729
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11277703_p23
|
PMC11277703
|
sec[1]/sec[4]/p[0]
|
2.5. Statistical Analysis
| 4.054688 |
biomedical
|
Study
|
[
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[
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] |
Positive percentage values were calculated for each distinct lesion within each sample. These values were then organized into tables for each animal group (control group and experimental groups A and B) and compared. To analyze the distribution pattern of antibody expression in relation to histological status, the lesions were categorized as histologically normal, precancerous lesions, benign tumors, or malignant tumors. To contrast the percentages of EGFR- and HER2-positive expression between groups A and B against the control group, as well as between histologically normal specimens and those exhibiting precancerous, benign, and malignant characteristics, the non-parametric Mann–Whitney test was employed due to the violation of normality assumptions as per the Kolmogorov–Smirnov criterion. All reported p -values were derived from two-tailed tests. Statistical significance was determined at a significance level of p < 0.05. The analyses were performed using SPSS software version 26.0.
|
[
"Georgia Vairaktari",
"Alexander Schramm",
"Efstathia Vairaktari",
"Spyridoula Derka",
"Andreas Sakkas",
"Nikolaos Lefantzis",
"Stavroula Diamantopoulou",
"Antonis Vylliotis",
"Andreas Lazaris",
"Marcel Ebeling",
"Stavros Vassiliou"
] |
https://doi.org/10.3390/jpm14070729
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11277703_p24
|
PMC11277703
|
sec[2]/p[0]
|
3. Results
| 2.425781 |
biomedical
|
Study
|
[
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] |
[
0.99365234375,
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0.0005917549133300781,
0.0005583763122558594
] |
The data from 459 biopsies were analyzed (8 from the control group, 211 from group A, and 240 from group B). Their histological statuses are presented in Table 1 separately.
|
[
"Georgia Vairaktari",
"Alexander Schramm",
"Efstathia Vairaktari",
"Spyridoula Derka",
"Andreas Sakkas",
"Nikolaos Lefantzis",
"Stavroula Diamantopoulou",
"Antonis Vylliotis",
"Andreas Lazaris",
"Marcel Ebeling",
"Stavros Vassiliou"
] |
https://doi.org/10.3390/jpm14070729
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277703_p25
|
PMC11277703
|
sec[2]/p[1]
|
3. Results
| 2.544922 |
biomedical
|
Study
|
[
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] |
[
0.99072265625,
0.0078125,
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] |
The percentage of NOTCH1-positive expression per animal is presented in Table 2 , by group.
|
[
"Georgia Vairaktari",
"Alexander Schramm",
"Efstathia Vairaktari",
"Spyridoula Derka",
"Andreas Sakkas",
"Nikolaos Lefantzis",
"Stavroula Diamantopoulou",
"Antonis Vylliotis",
"Andreas Lazaris",
"Marcel Ebeling",
"Stavros Vassiliou"
] |
https://doi.org/10.3390/jpm14070729
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11277703_p26
|
PMC11277703
|
sec[2]/p[2]
|
3. Results
| 3.550781 |
biomedical
|
Study
|
[
0.9990234375,
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] |
[
0.99853515625,
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0.0000928640365600586
] |
The mean percentage of positive expression for the control group was 0% (SD = 0%); for group A, it was 34.1% (SD = 25.1%); and for group B, it was 53.2% (SD = 17.8%) .
|
[
"Georgia Vairaktari",
"Alexander Schramm",
"Efstathia Vairaktari",
"Spyridoula Derka",
"Andreas Sakkas",
"Nikolaos Lefantzis",
"Stavroula Diamantopoulou",
"Antonis Vylliotis",
"Andreas Lazaris",
"Marcel Ebeling",
"Stavros Vassiliou"
] |
https://doi.org/10.3390/jpm14070729
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11277703_p27
|
PMC11277703
|
sec[2]/p[3]
|
3. Results
| 3.917969 |
biomedical
|
Study
|
[
0.9990234375,
0.00037026405334472656,
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] |
[
0.99951171875,
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0.00005549192428588867
] |
The mean percentages of NOTCH1-positive expression in groups A and B were significantly higher compared to the control group ( p < 0.001 for both comparisons). In group B, the mean percentage was significantly higher compared to group A ( p = 0.010).
|
[
"Georgia Vairaktari",
"Alexander Schramm",
"Efstathia Vairaktari",
"Spyridoula Derka",
"Andreas Sakkas",
"Nikolaos Lefantzis",
"Stavroula Diamantopoulou",
"Antonis Vylliotis",
"Andreas Lazaris",
"Marcel Ebeling",
"Stavros Vassiliou"
] |
https://doi.org/10.3390/jpm14070729
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277703_p28
|
PMC11277703
|
sec[2]/p[4]
|
3. Results
| 2.552734 |
biomedical
|
Study
|
[
0.99658203125,
0.0006041526794433594,
0.0027027130126953125
] |
[
0.99169921875,
0.006900787353515625,
0.0009479522705078125,
0.00023686885833740234
] |
The percentage of FGFR2-positive expression per animal is presented in Table 3 , for each group separately.
|
[
"Georgia Vairaktari",
"Alexander Schramm",
"Efstathia Vairaktari",
"Spyridoula Derka",
"Andreas Sakkas",
"Nikolaos Lefantzis",
"Stavroula Diamantopoulou",
"Antonis Vylliotis",
"Andreas Lazaris",
"Marcel Ebeling",
"Stavros Vassiliou"
] |
https://doi.org/10.3390/jpm14070729
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277703_p29
|
PMC11277703
|
sec[2]/p[5]
|
3. Results
| 3.558594 |
biomedical
|
Study
|
[
0.9990234375,
0.0004916191101074219,
0.00043702125549316406
] |
[
0.99853515625,
0.0010118484497070312,
0.00016105175018310547,
0.00009340047836303711
] |
The mean percentage of positive expression for the control group was 0% (SD = 0%); for group A, it was 41.5% (SD = 24.6%); and for group B, it was 58.8% (SD = 25.7%) .
|
[
"Georgia Vairaktari",
"Alexander Schramm",
"Efstathia Vairaktari",
"Spyridoula Derka",
"Andreas Sakkas",
"Nikolaos Lefantzis",
"Stavroula Diamantopoulou",
"Antonis Vylliotis",
"Andreas Lazaris",
"Marcel Ebeling",
"Stavros Vassiliou"
] |
https://doi.org/10.3390/jpm14070729
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277703_p30
|
PMC11277703
|
sec[2]/p[6]
|
3. Results
| 3.966797 |
biomedical
|
Study
|
[
0.9990234375,
0.0003638267517089844,
0.00038504600524902344
] |
[
0.99951171875,
0.0002796649932861328,
0.00020253658294677734,
0.000053048133850097656
] |
The mean percentages of FGFR2-positive expression in groups A and B were significantly higher compared to the control group ( p < 0.001 for both comparisons), while between groups A and B, the percentage of positive expression tended to be higher in group B ( p = 0.054).
|
[
"Georgia Vairaktari",
"Alexander Schramm",
"Efstathia Vairaktari",
"Spyridoula Derka",
"Andreas Sakkas",
"Nikolaos Lefantzis",
"Stavroula Diamantopoulou",
"Antonis Vylliotis",
"Andreas Lazaris",
"Marcel Ebeling",
"Stavros Vassiliou"
] |
https://doi.org/10.3390/jpm14070729
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277703_p31
|
PMC11277703
|
sec[2]/p[7]
|
3. Results
| 2.998047 |
biomedical
|
Study
|
[
0.998046875,
0.000522613525390625,
0.0011920928955078125
] |
[
0.99755859375,
0.0019350051879882812,
0.0003712177276611328,
0.00012314319610595703
] |
The percentages of NOTCH1- and FGFR2-positive expression, according to their histological status, are presented in Table 4 .
|
[
"Georgia Vairaktari",
"Alexander Schramm",
"Efstathia Vairaktari",
"Spyridoula Derka",
"Andreas Sakkas",
"Nikolaos Lefantzis",
"Stavroula Diamantopoulou",
"Antonis Vylliotis",
"Andreas Lazaris",
"Marcel Ebeling",
"Stavros Vassiliou"
] |
https://doi.org/10.3390/jpm14070729
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11277703_p32
|
PMC11277703
|
sec[2]/p[8]
|
3. Results
| 4.125 |
biomedical
|
Study
|
[
0.99951171875,
0.00028634071350097656,
0.0002359151840209961
] |
[
0.99951171875,
0.00015866756439208984,
0.0003509521484375,
0.00005835294723510742
] |
The mean percentage of NOTCH1-positive expression was 18.8% (standard deviation (SD) = 40.3%) in normal histology, 41.2% (SD = 50.7%) in malignant tumors, 44.6% (SD = 49.8%) in precancerous tumors, and 47.7% (SD = 50.2%) in benign tumors. A comparison of the mean percentages of NOTCH1-positive expression between histological statuses revealed that the positive expression in precancerous and benign tumors was significantly higher than that in normal histology ( p = 0.043 and p = 0.030, respectively). Furthermore, the mean percentage of NOTCH1-positive expression in malignant tumors was comparable to that of normal cases ( p = 0.168), and precancerous and benign tumors ( p = 0.0.785 and p = 0.615, respectively). The mean percentage of NOTCH1-positive expression in benign tumors was comparable to that in precancerous lesions ( p = 0.562). In the total sample, the mean percentage of FGFR2-positive cells was significantly greater than the corresponding percentage of NOTCH1-positive cells. This finding was also significant in malignant tumors and precancerous lesions, while no significant differences were found in normal histology and benign tumors.
|
[
"Georgia Vairaktari",
"Alexander Schramm",
"Efstathia Vairaktari",
"Spyridoula Derka",
"Andreas Sakkas",
"Nikolaos Lefantzis",
"Stavroula Diamantopoulou",
"Antonis Vylliotis",
"Andreas Lazaris",
"Marcel Ebeling",
"Stavros Vassiliou"
] |
https://doi.org/10.3390/jpm14070729
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11277703_p33
|
PMC11277703
|
sec[2]/p[9]
|
3. Results
| 4.097656 |
biomedical
|
Study
|
[
0.99951171875,
0.0002758502960205078,
0.00020253658294677734
] |
[
0.99951171875,
0.0001735687255859375,
0.00046825408935546875,
0.00006079673767089844
] |
The mean percentage of FGFR2-positive expression was 12.5% (SD = 34.2%) in normal histology, 76.5% (SD = 43.7%) in malignant tumors, 52.2% (SD = 50%) in precancerous lesions, and 50.4% (SD = 50.2%) in benign tumors. A significantly higher mean percentage of FGFR2-positive expression was found in malignant, precancerous, and benign tumors compared to normal histology ( p < 0.001, p = 0.002, and p = 0.008, respectively). Furthermore, the mean percentage of FGFR2-positive expression in malignant tumors was significantly greater than in precancerous and benign tumors ( p = 0.050 and p = 0.046, respectively). The mean percentage of FGFR2-positive expression in benign tumors was found to be similar to that observed in precancerous tumors ( p = 0.743).
|
[
"Georgia Vairaktari",
"Alexander Schramm",
"Efstathia Vairaktari",
"Spyridoula Derka",
"Andreas Sakkas",
"Nikolaos Lefantzis",
"Stavroula Diamantopoulou",
"Antonis Vylliotis",
"Andreas Lazaris",
"Marcel Ebeling",
"Stavros Vassiliou"
] |
https://doi.org/10.3390/jpm14070729
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277703_p34
|
PMC11277703
|
sec[2]/p[10]
|
3. Results
| 4.082031 |
biomedical
|
Study
|
[
0.99951171875,
0.00028228759765625,
0.00023221969604492188
] |
[
0.99951171875,
0.00015115737915039062,
0.0003094673156738281,
0.00005537271499633789
] |
To further support our findings, we conducted a detailed analysis of the expression patterns of NOTCH1 and FGFR2 across different histological stages. The mean percentage of NOTCH1-positive cells was highest in benign tumors (47.7%) and lowest in malignant tumors (18.8%), with precancerous lesions showing intermediate levels (41.2%). Conversely, FGFR2-positive cells were most abundant in precancerous (76.5%) and malignant tumors (52.2%), with lower levels in benign tumors (50.4%). These data underscore the inverse correlation between NOTCH1 and FGFR2 expression as tumors progress from the benign to malignant stages ( Table 4 ).
|
[
"Georgia Vairaktari",
"Alexander Schramm",
"Efstathia Vairaktari",
"Spyridoula Derka",
"Andreas Sakkas",
"Nikolaos Lefantzis",
"Stavroula Diamantopoulou",
"Antonis Vylliotis",
"Andreas Lazaris",
"Marcel Ebeling",
"Stavros Vassiliou"
] |
https://doi.org/10.3390/jpm14070729
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11277703_p35
|
PMC11277703
|
sec[2]/p[11]
|
3. Results
| 4.074219 |
biomedical
|
Study
|
[
0.99951171875,
0.00018584728240966797,
0.0002779960632324219
] |
[
0.99951171875,
0.0002224445343017578,
0.0002925395965576172,
0.00003838539123535156
] |
We have calculated both Spearman and Pearson correlation coefficients for NOTCH1 and FGFR2 expression in relation to tumor progression. The Spearman correlation coefficients are as follows: NOTCH1 and FGFR2 expression, 0.988; NOTCH1 expression and tumor progression, 0.953; and FGFR2 expression and tumor progression, 0.953. The Pearson correlation coefficients are as follows: NOTCH1 and FGFR2 expression, 0.988; NOTCH1 expression and tumor progression, 0.950; and FGFR2 expression and tumor progression, 0.948. These correlation coefficients indicate a strong positive correlation between NOTCH1 and FGFR2 expression and their relationship with tumor progression, supporting our reported findings.
|
[
"Georgia Vairaktari",
"Alexander Schramm",
"Efstathia Vairaktari",
"Spyridoula Derka",
"Andreas Sakkas",
"Nikolaos Lefantzis",
"Stavroula Diamantopoulou",
"Antonis Vylliotis",
"Andreas Lazaris",
"Marcel Ebeling",
"Stavros Vassiliou"
] |
https://doi.org/10.3390/jpm14070729
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11277703_p36
|
PMC11277703
|
sec[3]/p[0]
|
4. Discussion
| 4.167969 |
biomedical
|
Study
|
[
0.99951171875,
0.00037550926208496094,
0.00018739700317382812
] |
[
0.99951171875,
0.00019478797912597656,
0.0004229545593261719,
0.00007992982864379883
] |
The intent of this study was to evaluate the expression patterns of the NOTCH1 and FGFR2 genes and to explore potential correlations between them across successive histological stages of cutaneous squamous cell carcinoma. It was assumed that the expression of the investigated genes increases as the degree of tissue dedifferentiation increases. This hypothesis was at least partially confirmed. The mouse model for skin carcinogenesis has played a crucial role in understanding how human epithelial cancers develop . By conducting multistage experiments on mice skin, researchers can gain insights applicable to both scientific investigation and clinical treatment, potentially leading to innovative approaches in managing skin cancer. The identification of oncogenes in human cancers has significantly advanced our comprehension of the disease, with these molecular markers holding promise for therapy, early detection, and prognosis. Our research consortium has developed animal models to study the molecular alterations leading to the onset of oral squamous cell carcinomas in rodents. These models were pioneered based on our prior expertise . Based on this foundational knowledge, we conducted a two-stage in vivo carcinogenesis investigation using FVB/N mice skin as our experimental substrate. Our primary focus was to determine the expression patterns of NOTCH1 and FGFR2 oncogenes across all discernible histological stages. The examination of skin lesions in our experimental groups closely followed the progression of tumor development, from dysplasia to poorly differentiated carcinoma.
|
[
"Georgia Vairaktari",
"Alexander Schramm",
"Efstathia Vairaktari",
"Spyridoula Derka",
"Andreas Sakkas",
"Nikolaos Lefantzis",
"Stavroula Diamantopoulou",
"Antonis Vylliotis",
"Andreas Lazaris",
"Marcel Ebeling",
"Stavros Vassiliou"
] |
https://doi.org/10.3390/jpm14070729
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277703_p37
|
PMC11277703
|
sec[3]/p[1]
|
4. Discussion
| 3.460938 |
biomedical
|
Study
|
[
0.99853515625,
0.00025534629821777344,
0.0012350082397460938
] |
[
0.9833984375,
0.0156097412109375,
0.0008673667907714844,
0.00021386146545410156
] |
It could be shown that a longer treatment with 7,12-dimethylbenz[a]anthracene (DMBA) and 12-O-tetradecanoyl phorbol-13-acetate (TPA) leads to a percentage increase in the development of malignant lesions.
|
[
"Georgia Vairaktari",
"Alexander Schramm",
"Efstathia Vairaktari",
"Spyridoula Derka",
"Andreas Sakkas",
"Nikolaos Lefantzis",
"Stavroula Diamantopoulou",
"Antonis Vylliotis",
"Andreas Lazaris",
"Marcel Ebeling",
"Stavros Vassiliou"
] |
https://doi.org/10.3390/jpm14070729
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11277703_p38
|
PMC11277703
|
sec[3]/p[2]
|
4. Discussion
| 4.195313 |
biomedical
|
Study
|
[
0.99951171875,
0.000308990478515625,
0.00020301342010498047
] |
[
0.9990234375,
0.0001735687255859375,
0.000522613525390625,
0.00007611513137817383
] |
In our study, we observed distinct expression patterns of NOTCH1 and FGFR2 across different histological stages of cutaneous squamous cell carcinoma (cSCC). Notably, NOTCH1 expression was higher in benign tumors compared to precancerous and malignant tumors, whereas FGFR2 expression showed an opposite trend, with higher levels in precancerous and malignant tumors compared to benign tumors. The elevated NOTCH1 expression in benign tumors suggests a potential role in the early stages of tumorigenesis. Previous studies have indicated that NOTCH1 can function as a tumor suppressor in skin, where its activation may inhibit keratinocyte proliferation and promote differentiation. This tumor-suppressive activity could explain the higher NOTCH1 levels observed in benign tumors, which are less aggressive and more differentiated compared to its malignant counterparts. For example, Radtke et al. demonstrated that Notch1 deficiency in skin and primary keratinocytes leads to the development of basal-cell carcinoma-like tumors due to sustained Gli2 expression .
|
[
"Georgia Vairaktari",
"Alexander Schramm",
"Efstathia Vairaktari",
"Spyridoula Derka",
"Andreas Sakkas",
"Nikolaos Lefantzis",
"Stavroula Diamantopoulou",
"Antonis Vylliotis",
"Andreas Lazaris",
"Marcel Ebeling",
"Stavros Vassiliou"
] |
https://doi.org/10.3390/jpm14070729
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11277703_p39
|
PMC11277703
|
sec[3]/p[3]
|
4. Discussion
| 4.429688 |
biomedical
|
Study
|
[
0.99951171875,
0.0003199577331542969,
0.000202178955078125
] |
[
0.99609375,
0.0003714561462402344,
0.0033359527587890625,
0.00014603137969970703
] |
In contrast, FGFR2 was significantly elevated in precancerous and malignant tumors, indicating its role in the progression and aggressiveness of cSCC. FGFR2 activation is known to promote oncogenic pathways such as the MAPK and PI3K/AKT signaling cascades, which enhance cell proliferation, survival, and migration. The high FGFR2 expression in more advanced tumor stages aligns with its role in driving tumorigenesis and supporting the malignant phenotype. Grose et al. found that conditional FGFR2b knockout in murine epidermis increased SCC incidence, underscoring FGFR2’s role in tumor development. The observed opposite trends in NOTCH1 and FGFR2 expression can be attributed to their distinct roles in tumor biology. While NOTCH1’s tumor-suppressive functions are more prominent in the initial, less aggressive stages of tumor formation, FGFR2’s oncogenic activities drive tumor progression and malignancy. This dichotomy highlights the complex interplay between different signaling pathways in cSCC and suggests potential therapeutic targets at various stages of the disease.
|
[
"Georgia Vairaktari",
"Alexander Schramm",
"Efstathia Vairaktari",
"Spyridoula Derka",
"Andreas Sakkas",
"Nikolaos Lefantzis",
"Stavroula Diamantopoulou",
"Antonis Vylliotis",
"Andreas Lazaris",
"Marcel Ebeling",
"Stavros Vassiliou"
] |
https://doi.org/10.3390/jpm14070729
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11277703_p40
|
PMC11277703
|
sec[3]/p[4]
|
4. Discussion
| 2.507813 |
biomedical
|
Study
|
[
0.99658203125,
0.0006356239318847656,
0.002666473388671875
] |
[
0.923828125,
0.060699462890625,
0.01427459716796875,
0.0011339187622070312
] |
Our findings on the involvement of NOTCH1 in skin cancer development are consistent with those in the current literature.
|
[
"Georgia Vairaktari",
"Alexander Schramm",
"Efstathia Vairaktari",
"Spyridoula Derka",
"Andreas Sakkas",
"Nikolaos Lefantzis",
"Stavroula Diamantopoulou",
"Antonis Vylliotis",
"Andreas Lazaris",
"Marcel Ebeling",
"Stavros Vassiliou"
] |
https://doi.org/10.3390/jpm14070729
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277703_p41
|
PMC11277703
|
sec[3]/p[5]
|
4. Discussion
| 4.125 |
biomedical
|
Study
|
[
0.99951171875,
0.00020420551300048828,
0.00017333030700683594
] |
[
0.98486328125,
0.0005278587341308594,
0.01462554931640625,
0.00014770030975341797
] |
Wang et al. demonstrated through immunofluorescence and Western blot analysis that NOTCH1 is upregulated in skin cancer tissues . The inhibition or activation of NOTCH1 resulted in an altered expression of E-cadherin in the experimental setup, such as changes in DNA methylation. Moreover, it has been demonstrated that the migration and invasion of tumor cells are affected by the activation or inhibition of NOTCH1. Therefore, NOTCH1 is a promising target for personalized and targeted therapies for skin cancer. Kopan et al. conducted experiments that revealed that the non-cell autonomous consequences of defective barrier formation are responsible for the tumor-promoting effects of Notch1 loss in mouse skin.
|
[
"Georgia Vairaktari",
"Alexander Schramm",
"Efstathia Vairaktari",
"Spyridoula Derka",
"Andreas Sakkas",
"Nikolaos Lefantzis",
"Stavroula Diamantopoulou",
"Antonis Vylliotis",
"Andreas Lazaris",
"Marcel Ebeling",
"Stavros Vassiliou"
] |
https://doi.org/10.3390/jpm14070729
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277703_p42
|
PMC11277703
|
sec[3]/p[6]
|
4. Discussion
| 4.359375 |
biomedical
|
Study
|
[
0.9990234375,
0.0004172325134277344,
0.00035071372985839844
] |
[
0.87255859375,
0.00139617919921875,
0.1256103515625,
0.0005125999450683594
] |
However, the understanding of FGFR2 expression remains unclear. FGFR2 is a receptor tyrosine kinase implicated in various cellular processes, including proliferation, differentiation, and survival. Aberrant FGFR2 signaling has been linked to tumorigenesis in several cancers, including breast, gastric, and endometrial cancers, through the activation of downstream pathways such as MAPK, PI3K/AKT, and STAT signaling cascades. In the context of cSCC, FGFR2 gene amplification and mutations can lead to its constitutive activation, promoting oncogenic pathways that contribute to skin carcinogenesis . Recent studies have shown that selective FGFR inhibitors, such as AZD4547, can reduce UVB-induced FGFR2 activation and subsequent epidermal hyperplasia, highlighting its potential as a therapeutic target in cSCC. Despite these findings, further research is needed to fully understand the specific role and mechanisms of FGFR2 in cSCC . We have updated the Section 4 Discussion to include these insights and relevant references to provide a more comprehensive understanding of FGFR2’s involvement in cSCC. Grose et al. demonstrated that conditional FGFR2b knockout within the epidermis of murine models resulted in an increased incidence of SCCs , which contrasts with Nan et al.’s findings. Nan et al.’s investigation found no evidence implicating genetic variants in FGFR2 or FGFR4 genes in contributing to the hereditary predisposition to skin cancer among Caucasian women .
|
[
"Georgia Vairaktari",
"Alexander Schramm",
"Efstathia Vairaktari",
"Spyridoula Derka",
"Andreas Sakkas",
"Nikolaos Lefantzis",
"Stavroula Diamantopoulou",
"Antonis Vylliotis",
"Andreas Lazaris",
"Marcel Ebeling",
"Stavros Vassiliou"
] |
https://doi.org/10.3390/jpm14070729
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11277703_p43
|
PMC11277703
|
sec[3]/p[7]
|
4. Discussion
| 4.175781 |
biomedical
|
Study
|
[
0.99951171875,
0.00028395652770996094,
0.0002359151840209961
] |
[
0.99853515625,
0.00018107891082763672,
0.0010480880737304688,
0.00007146596908569336
] |
While our study provides significant insights into the expression patterns of NOTCH1 and FGFR2 in cutaneous squamous cell carcinoma (cSCC), there are several limitations to consider. The sample size, especially of the control group, was relatively small, which might affect the robustness of the statistical analyses. Future research should aim to include larger sample sizes and more balanced group distributions to ensure more robust and statistically sound comparisons. A further limitation of this study is the exclusive use of female FVB/N mice. This was a deliberate choice to maintain consistency in hormonal profiles and to avoid potential hormonal fluctuations in male mice. However, this restricts the generalizability of our findings to male subjects. Future studies incorporating male mice would be essential to comprehensively understand any potential sex-specific differences in the activation of NOTCH1 and FGFR2 oncogenes and their role in skin cancer induction. Furthermore, investigating the impact of sex hormones on these pathways could offer valuable insights into the underlying mechanisms of oncogene activation in skin carcinogenesis, despite the challenges of housing male mice and the potential for aggression. In conclusion, while our findings are promising, they highlight the need for additional research to explore these limitations. Future studies should focus on incorporating a broader range of samples, including both sexes, and employing molecular techniques to deepen our understanding of the genetic and epigenetic mechanisms driving cSCC.
|
[
"Georgia Vairaktari",
"Alexander Schramm",
"Efstathia Vairaktari",
"Spyridoula Derka",
"Andreas Sakkas",
"Nikolaos Lefantzis",
"Stavroula Diamantopoulou",
"Antonis Vylliotis",
"Andreas Lazaris",
"Marcel Ebeling",
"Stavros Vassiliou"
] |
https://doi.org/10.3390/jpm14070729
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999999 |
PMC11277703_p44
|
PMC11277703
|
sec[3]/p[8]
|
4. Discussion
| 3.90625 |
biomedical
|
Study
|
[
0.99951171875,
0.00016963481903076172,
0.00034999847412109375
] |
[
0.92919921875,
0.0036373138427734375,
0.067138671875,
0.0002338886260986328
] |
However, it is important to interpret these findings cautiously due to the limitations discussed above. The harvested data support the hypotheses of activity of Notch1 and FGFR2 throughout various stages of tumorigenesis, spanning from initial oncogenic phases to advanced malignancies. Additionally, a clear correlation between FGFR2 and the progression of cutaneous neoplasms is revealed, while NOTCH 1 is inversely correlated. This may encourage further research. If these results are confirmed in future applications for the diagnosis, treatment, or prognosis of skin cancer, they may become more significant.
|
[
"Georgia Vairaktari",
"Alexander Schramm",
"Efstathia Vairaktari",
"Spyridoula Derka",
"Andreas Sakkas",
"Nikolaos Lefantzis",
"Stavroula Diamantopoulou",
"Antonis Vylliotis",
"Andreas Lazaris",
"Marcel Ebeling",
"Stavros Vassiliou"
] |
https://doi.org/10.3390/jpm14070729
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277703_p45
|
PMC11277703
|
sec[4]/p[0]
|
5. Conclusions
| 4.046875 |
biomedical
|
Study
|
[
0.99951171875,
0.0001881122589111328,
0.00016999244689941406
] |
[
0.9990234375,
0.00028443336486816406,
0.0006060600280761719,
0.00007164478302001953
] |
The animal model showcased here holds promise as a valuable resource for unraveling the involvement of additional genes in skin cancer development. Our study revealed a clear correlation of FGFR2 and the progression of cutaneous neoplasms, while NOTCH 1 is inversely correlated. These results hint at a potential early engagement of these oncogenes in driving the advancement of skin tumors within this model. Nevertheless, further studies with male and female mice are necessary to validate our results in the future.
|
[
"Georgia Vairaktari",
"Alexander Schramm",
"Efstathia Vairaktari",
"Spyridoula Derka",
"Andreas Sakkas",
"Nikolaos Lefantzis",
"Stavroula Diamantopoulou",
"Antonis Vylliotis",
"Andreas Lazaris",
"Marcel Ebeling",
"Stavros Vassiliou"
] |
https://doi.org/10.3390/jpm14070729
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
39057647_p0
|
39057647
|
sec[0]/p[0]
|
1. Introduction
| 4.042969 |
biomedical
|
Review
|
[
0.99755859375,
0.001529693603515625,
0.0009703636169433594
] |
[
0.1817626953125,
0.0015783309936523438,
0.81591796875,
0.0005288124084472656
] |
Although several studies have evaluated aortic valve replacement (AVR) outcomes using different valve prostheses, the valve choice remains challenging . The risk of bleeding associated with anticoagulation therapy and possible teratogenic risk for women of childbearing age are two obstacles to consider before deciding to implant a mechanical valve . Mechanical aortic valves were associated with greater bleeding rates than bioprosthetic valves in patients aged 50 to 69 years , consistent with studies on mechanical mitral valves . Regarding bioprosthetic valve selection, structural valve deterioration and lower durability requiring reoperation are among the most feared drawbacks despite the acceptable five-year durability of bioprosthetic AVR . Earlier studies showed similar survival rates with mechanical or bioprosthetic AVR .
|
[
"Fatimah A. Alhijab",
"Latifa A. Alfayez",
"Essam Hassan",
"Monirah A. Albabtain",
"Ismail M. Elnaggar",
"Khaled A. Alotaibi",
"Adam I. Adam",
"Claudio Pragliola",
"Huda H. Ismail",
"Amr A. Arafat"
] |
https://doi.org/10.3390/jcdd11070227
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
39057647_p1
|
39057647
|
sec[0]/p[1]
|
1. Introduction
| 3.935547 |
biomedical
|
Review
|
[
0.998046875,
0.001232147216796875,
0.0008206367492675781
] |
[
0.08795166015625,
0.004070281982421875,
0.9072265625,
0.0005469322204589844
] |
On the other hand, recent studies reported similar risks of bleeding and stroke between mechanical and bioprosthetic valves, with better long-term survival in patients with mechanical valves . Recently, the introduction of new generations of bioprosthetic aortic valves with comparable costs to mechanical valves and transcatheter aortic valve interventions has increased the popularity of bioprosthetic valves. Moreover, lower anticoagulation intensity in patients with mechanical aortic valves might promote mechanical valve use in older patients .
|
[
"Fatimah A. Alhijab",
"Latifa A. Alfayez",
"Essam Hassan",
"Monirah A. Albabtain",
"Ismail M. Elnaggar",
"Khaled A. Alotaibi",
"Adam I. Adam",
"Claudio Pragliola",
"Huda H. Ismail",
"Amr A. Arafat"
] |
https://doi.org/10.3390/jcdd11070227
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
39057647_p2
|
39057647
|
sec[0]/p[2]
|
1. Introduction
| 4.136719 |
biomedical
|
Study
|
[
0.99755859375,
0.0023365020751953125,
0.00023090839385986328
] |
[
0.998046875,
0.0011548995971679688,
0.0005583763122558594,
0.0002586841583251953
] |
Despite recent advances in aortic valve interventions through transcatheter and minimally invasive surgery , choosing an aortic valve prosthesis is challenging in young and old patients. Patients with rheumatic valve disease might require valve replacement at a young age. Bioprosthetic valves have the advantage of preventing anticoagulation during pregnancy; however, the risk of multiple reoperations is substantial. Therefore, further studies are required to explore the long-term differences between the two types of valves, especially in our Middle Eastern population, which has a high incidence of rheumatic heart disease requiring surgery at a young age. In this study, we aimed to investigate long-term outcomes in adult patients older or younger than 50 years after AVR with mechanical or bioprosthetic valves. Furthermore, we characterized patients who received mechanical and bioprosthetic valves in patients older or younger than 50 years.
|
[
"Fatimah A. Alhijab",
"Latifa A. Alfayez",
"Essam Hassan",
"Monirah A. Albabtain",
"Ismail M. Elnaggar",
"Khaled A. Alotaibi",
"Adam I. Adam",
"Claudio Pragliola",
"Huda H. Ismail",
"Amr A. Arafat"
] |
https://doi.org/10.3390/jcdd11070227
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
39057647_p3
|
39057647
|
sec[1]/sec[0]/p[0]
|
2.1. Study Design and Patients
| 4.136719 |
biomedical
|
Study
|
[
0.99462890625,
0.005069732666015625,
0.0002682209014892578
] |
[
0.99755859375,
0.0010251998901367188,
0.0007982254028320312,
0.0004673004150390625
] |
We conducted a retrospective cohort study that included 292 patients who underwent isolated AVR from 2009 to 2020 at Prince Sultan Cardiac Center, Riyadh, Saudi Arabia. We grouped the patients according to their age (≤50 years and >50 years) and type of implanted aortic valve (mechanical or bioprosthetic aortic valve). The groups included patients older than 50 years with either bioprosthetic (Group 1a: n = 111) or mechanical AVR (Group 2a: n = 38) and patients aged ≤50 years with bioprosthetic (Group 1b: n = 48) or mechanical AVR (Group 2b: n = 95). Patients who underwent AVR and concomitant coronary artery bypass grafting (CABG), mitral or tricuspid valve surgery, or other cardiac procedures were excluded from this study. Age older than 50 is the recommended age for the possibility of using bioprosthetic valves in the aortic position . This study included patients with primary or redo AVR because this could be a factor that affected prostheses choice.
|
[
"Fatimah A. Alhijab",
"Latifa A. Alfayez",
"Essam Hassan",
"Monirah A. Albabtain",
"Ismail M. Elnaggar",
"Khaled A. Alotaibi",
"Adam I. Adam",
"Claudio Pragliola",
"Huda H. Ismail",
"Amr A. Arafat"
] |
https://doi.org/10.3390/jcdd11070227
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
39057647_p4
|
39057647
|
sec[1]/sec[0]/p[1]
|
2.1. Study Design and Patients
| 1.022461 |
biomedical
|
Other
|
[
0.77099609375,
0.00849151611328125,
0.220703125
] |
[
0.0226593017578125,
0.974609375,
0.00113677978515625,
0.0015840530395507812
] |
Approval for this study was obtained from the Institutional Review Board , and the need for patient consent was waived.
|
[
"Fatimah A. Alhijab",
"Latifa A. Alfayez",
"Essam Hassan",
"Monirah A. Albabtain",
"Ismail M. Elnaggar",
"Khaled A. Alotaibi",
"Adam I. Adam",
"Claudio Pragliola",
"Huda H. Ismail",
"Amr A. Arafat"
] |
https://doi.org/10.3390/jcdd11070227
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
39057647_p5
|
39057647
|
sec[1]/sec[1]/p[0]
|
2.2. Study Data and Outcomes
| 4.085938 |
biomedical
|
Study
|
[
0.94921875,
0.050262451171875,
0.0006470680236816406
] |
[
0.9892578125,
0.005489349365234375,
0.002349853515625,
0.002685546875
] |
Demographic, clinical, laboratory, and echocardiographic data were collected from paper and electronic medical charts. Preoperative data included age, body mass index (BMI), sex, EuroSCORE II, New York Heart Association class (NYHA), hypertension, diabetes mellitus (DM), chronic lung disease, renal impairment, liver disease, previous myocardial infarction (MI), previous heart failure hospitalization within one year prior to surgery, old stroke, atrial fibrillation (AF), previous cardiac surgery, previous percutaneous coronary intervention (PCI), previous transcatheter aortic valve replacement, hemoglobin level, and creatinine clearance. Operative data included emergency status (critical aortic stenosis or stuck aortic prosthesis), cardiopulmonary bypass (CPB), and cross-clamp times. Postoperative outcomes included hospital mortality, return to the operating room for bleeding, blood transfusion, early permanent pacemaker insertion (PPM), new-onset AF, stroke, MI, creatinine level (highest before discharge), respiratory failure, length of ICU, and length of hospital stay. The long-term outcomes were mortality, stroke, need for valve reintervention, bleeding, and cardiac rehospitalization for heart failure.
|
[
"Fatimah A. Alhijab",
"Latifa A. Alfayez",
"Essam Hassan",
"Monirah A. Albabtain",
"Ismail M. Elnaggar",
"Khaled A. Alotaibi",
"Adam I. Adam",
"Claudio Pragliola",
"Huda H. Ismail",
"Amr A. Arafat"
] |
https://doi.org/10.3390/jcdd11070227
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
39057647_p6
|
39057647
|
sec[1]/sec[2]/p[0]
|
2.3. Outcomes
| 3.644531 |
clinical
|
Other
|
[
0.4873046875,
0.50537109375,
0.00733184814453125
] |
[
0.4345703125,
0.54736328125,
0.0032672882080078125,
0.014801025390625
] |
The primary endpoint was all-cause mortality during hospitalization or at follow-up. The secondary endpoints were major adverse events in the hospital and follow-up. Other secondary outcomes included all bleeding, stroke, and aortic valve reintervention.
|
[
"Fatimah A. Alhijab",
"Latifa A. Alfayez",
"Essam Hassan",
"Monirah A. Albabtain",
"Ismail M. Elnaggar",
"Khaled A. Alotaibi",
"Adam I. Adam",
"Claudio Pragliola",
"Huda H. Ismail",
"Amr A. Arafat"
] |
https://doi.org/10.3390/jcdd11070227
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
39057647_p7
|
39057647
|
sec[1]/sec[3]/p[0]
|
2.4. Echocardiography
| 3.810547 |
biomedical
|
Study
|
[
0.986328125,
0.0134124755859375,
0.00044608116149902344
] |
[
0.99560546875,
0.0027141571044921875,
0.0006437301635742188,
0.0008187294006347656
] |
All patients underwent transthoracic echocardiograms before surgery and at discharge. Changes in the ejection fraction (EF), peak aortic valve pressure, and LV mass were reported and compared between the groups.
|
[
"Fatimah A. Alhijab",
"Latifa A. Alfayez",
"Essam Hassan",
"Monirah A. Albabtain",
"Ismail M. Elnaggar",
"Khaled A. Alotaibi",
"Adam I. Adam",
"Claudio Pragliola",
"Huda H. Ismail",
"Amr A. Arafat"
] |
https://doi.org/10.3390/jcdd11070227
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
39057647_p8
|
39057647
|
sec[1]/sec[4]/p[0]
|
2.5. Prosthesis Types
| 2.755859 |
biomedical
|
Other
|
[
0.99658203125,
0.002803802490234375,
0.0008420944213867188
] |
[
0.4140625,
0.58056640625,
0.002605438232421875,
0.002895355224609375
] |
The mechanical valves used in our study were St. Jude mechanical valves (SJM; St. Jude Medical Inc.; Minneapolis, MN, USA), ATS (Medtronic; Minneapolis, MN, USA), Carbomedics Sorin (LivaNova PLC, Sorin, Sluggia, Italy), and On-X (CryoLife, Kennesaw, GA, USA). Tissue valves were Magna valves (Edwards Lifesciences, Irvine, CA, USA), Trifecta (Abbott, Plymouth, MN, USA), Perceval sutureless valves (LivaNova Group, Milan, Italy), and Hancock (Medtronic Inc.; Minneapolis, MN, USA).
|
[
"Fatimah A. Alhijab",
"Latifa A. Alfayez",
"Essam Hassan",
"Monirah A. Albabtain",
"Ismail M. Elnaggar",
"Khaled A. Alotaibi",
"Adam I. Adam",
"Claudio Pragliola",
"Huda H. Ismail",
"Amr A. Arafat"
] |
https://doi.org/10.3390/jcdd11070227
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
39057647_p9
|
39057647
|
sec[1]/sec[5]/p[0]
|
2.6. Follow-Up
| 3.431641 |
clinical
|
Other
|
[
0.12042236328125,
0.8779296875,
0.00176239013671875
] |
[
0.277099609375,
0.371826171875,
0.006465911865234375,
0.344482421875
] |
All patients were clinically followed up in our outpatient clinic at 1, 6, and 12 months postoperatively and at yearly intervals thereafter. The patient’s vital status was confirmed by phone in June 2021 and by reviewing the medical records for all patients in June 2023. The hospital anticoagulation protocol was the same for mechanical and bioprosthetic valves. Patients were discharged on warfarin after achieving the target INR. and followed up in the anticoagulation clinic. The target INR was 2–3 for the mechanical valves for life, and patients with bioprosthetic valves had warfarin for only three months. Patients with bioprosthetic valves and contraindications to warfarin were discharged on aspirin only.
|
[
"Fatimah A. Alhijab",
"Latifa A. Alfayez",
"Essam Hassan",
"Monirah A. Albabtain",
"Ismail M. Elnaggar",
"Khaled A. Alotaibi",
"Adam I. Adam",
"Claudio Pragliola",
"Huda H. Ismail",
"Amr A. Arafat"
] |
https://doi.org/10.3390/jcdd11070227
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
39057647_p10
|
39057647
|
sec[1]/sec[6]/p[0]
|
2.7. Definitions
| 2.669922 |
biomedical
|
Study
|
[
0.9130859375,
0.083740234375,
0.003261566162109375
] |
[
0.96875,
0.0261383056640625,
0.0015172958374023438,
0.0037441253662109375
] |
Hospital outcomes were defined as those occurring 30 days after surgery or within the same hospital admission. Preoperative variables were collected according to EuroSCORE II definitions .
|
[
"Fatimah A. Alhijab",
"Latifa A. Alfayez",
"Essam Hassan",
"Monirah A. Albabtain",
"Ismail M. Elnaggar",
"Khaled A. Alotaibi",
"Adam I. Adam",
"Claudio Pragliola",
"Huda H. Ismail",
"Amr A. Arafat"
] |
https://doi.org/10.3390/jcdd11070227
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
39057647_p11
|
39057647
|
sec[1]/sec[7]/p[0]
|
2.8. Statistical Analysis
| 3.923828 |
biomedical
|
Study
|
[
0.9990234375,
0.00024819374084472656,
0.0004982948303222656
] |
[
0.998046875,
0.0014591217041015625,
0.00035500526428222656,
0.00006669759750366211
] |
We used Stata 18 (Stata Corp, College Station, TX, USA) to perform all the statistical analyses. The Shapiro–Wilk test was used to test the distribution of the continuous variables. Normally distributed data are expressed as the mean and standard deviation and were compared with Student’s t-test. Nonnormal data are expressed as medians (25th–75th percentiles) and were compared with the Mann–Whitney test. Categorical data are presented as frequencies and percentages and were compared with Fisher’s exact test if the expected frequency was less than five. Survival distribution was plotted using Kaplan–Meier curves and compared with the log-rank test. The random effect model was used to compare the repeated measures among groups. A two-sided p -value of less than 0.05 was considered to indicate statistical significance.
|
[
"Fatimah A. Alhijab",
"Latifa A. Alfayez",
"Essam Hassan",
"Monirah A. Albabtain",
"Ismail M. Elnaggar",
"Khaled A. Alotaibi",
"Adam I. Adam",
"Claudio Pragliola",
"Huda H. Ismail",
"Amr A. Arafat"
] |
https://doi.org/10.3390/jcdd11070227
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
39057647_p12
|
39057647
|
sec[2]/sec[0]/p[0]
|
3.1. Baseline and Operative Characteristics
| 4.128906 |
biomedical
|
Study
|
[
0.98876953125,
0.01056671142578125,
0.0004930496215820312
] |
[
0.99658203125,
0.00217437744140625,
0.0005903244018554688,
0.00046706199645996094
] |
A greater proportion of male participants were in Group 2b ( p = 0.018). The groups had no significant difference in body mass index (BMI). The EuroSCORE II was significantly greater in Group 2a than in Group 2b (0.94% vs. 0.87%, p = 0.049). The prevalence of hypertension and old stroke was significantly greater in Group 2a than in Group 2b. The groups had nearly equal rates of other preexisting comorbidities, with no significant differences observed between the groups in terms of smoking status, renal impairment status, diabetes status, liver disease status, chronic lung disease status, previous MI status, previous heart failure hospitalization status, AF status, previous cardiac surgery status, previous PCI status or previous transcatheter aortic valve intervention (TAVI) status. Patients in Group 1a had significantly lower hemoglobin levels and creatinine clearance levels than those in Group 2b.
|
[
"Fatimah A. Alhijab",
"Latifa A. Alfayez",
"Essam Hassan",
"Monirah A. Albabtain",
"Ismail M. Elnaggar",
"Khaled A. Alotaibi",
"Adam I. Adam",
"Claudio Pragliola",
"Huda H. Ismail",
"Amr A. Arafat"
] |
https://doi.org/10.3390/jcdd11070227
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
39057647_p13
|
39057647
|
sec[2]/sec[0]/p[1]
|
3.1. Baseline and Operative Characteristics
| 3.337891 |
biomedical
|
Study
|
[
0.9599609375,
0.038909912109375,
0.0009579658508300781
] |
[
0.98828125,
0.007904052734375,
0.0012178421020507812,
0.002613067626953125
] |
Moreover, the groups had similar presentations, with no significant difference in the NYHA class ( Table 1 ). There was no difference in the operative status between patients who underwent AVR tissue or mechanical surgery, regardless of their age group. The groups had no difference in cardiopulmonary bypass and ischemic times ( Table 1 ).
|
[
"Fatimah A. Alhijab",
"Latifa A. Alfayez",
"Essam Hassan",
"Monirah A. Albabtain",
"Ismail M. Elnaggar",
"Khaled A. Alotaibi",
"Adam I. Adam",
"Claudio Pragliola",
"Huda H. Ismail",
"Amr A. Arafat"
] |
https://doi.org/10.3390/jcdd11070227
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
39057647_p14
|
39057647
|
sec[2]/sec[1]/p[0]
|
3.2. Echocardiographic Characteristics
| 4.027344 |
biomedical
|
Study
|
[
0.99267578125,
0.006755828857421875,
0.0003376007080078125
] |
[
0.9970703125,
0.00121307373046875,
0.0008831024169921875,
0.0006475448608398438
] |
There was no difference in the preoperative ejection fraction between the groups. Ventricular mass and peak velocity did not vary significantly among the presented groups. Patients had similar end-diastolic and end-systolic diameters. There was no significant difference between participants regarding pulmonary artery systolic pressure, the severity of aortic valve regurgitation, or the severity of aortic valve stenosis ( Table 2 ).
|
[
"Fatimah A. Alhijab",
"Latifa A. Alfayez",
"Essam Hassan",
"Monirah A. Albabtain",
"Ismail M. Elnaggar",
"Khaled A. Alotaibi",
"Adam I. Adam",
"Claudio Pragliola",
"Huda H. Ismail",
"Amr A. Arafat"
] |
https://doi.org/10.3390/jcdd11070227
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
39057647_p15
|
39057647
|
sec[2]/sec[2]/p[0]
|
3.3. Postoperative Complications
| 4.109375 |
biomedical
|
Study
|
[
0.96337890625,
0.03570556640625,
0.0007371902465820312
] |
[
0.994140625,
0.00354766845703125,
0.00091552734375,
0.0012884140014648438
] |
Re-exploration for bleeding was more common in patients older than 50 years who underwent mechanical AVR (Group 2a) ( p = 0.045). There was no difference in other postoperative complications between the groups. The hospital mortality rate was not significantly different among the studied groups. There were 4 deaths (3.6%) in Group 1a and 2 (5.26%) in Group 2a. However, there were no deaths among patients who were 50 years of age or younger and who underwent aortic valve replacement with a tissue valve, while there were no cases (2.11%) of deaths among patients who underwent mechanical valve replacement ( p = 0.551) ( Table 3 ).
|
[
"Fatimah A. Alhijab",
"Latifa A. Alfayez",
"Essam Hassan",
"Monirah A. Albabtain",
"Ismail M. Elnaggar",
"Khaled A. Alotaibi",
"Adam I. Adam",
"Claudio Pragliola",
"Huda H. Ismail",
"Amr A. Arafat"
] |
https://doi.org/10.3390/jcdd11070227
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
39057647_p16
|
39057647
|
sec[2]/sec[3]/p[0]
|
3.4. Survival Rates
| 4.019531 |
biomedical
|
Study
|
[
0.90380859375,
0.0946044921875,
0.0014324188232421875
] |
[
0.958984375,
0.03570556640625,
0.001567840576171875,
0.0036640167236328125
] |
The median follow-up time was 45 months (22–72) for patients > 50 years. Survival at 5 and 10 years was 88% and 81% in Group 1a and 89% and 89%, respectively, in Group 2b. The total mortality rate was 9% (10 patients) in Group 1a and 10.5% (4 patients) in Group 2a. The median follow-up in patients ≤ 50 years was 56 (19–85) months. Survival in Group 1b was 100%, and that in Group 2b was 98% at 5 years and 95% at 10 years .
|
[
"Fatimah A. Alhijab",
"Latifa A. Alfayez",
"Essam Hassan",
"Monirah A. Albabtain",
"Ismail M. Elnaggar",
"Khaled A. Alotaibi",
"Adam I. Adam",
"Claudio Pragliola",
"Huda H. Ismail",
"Amr A. Arafat"
] |
https://doi.org/10.3390/jcdd11070227
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
39057647_p17
|
39057647
|
sec[2]/sec[4]/p[0]
|
3.5. Freedom from Reintervention
| 4.070313 |
biomedical
|
Study
|
[
0.84033203125,
0.157958984375,
0.0017070770263671875
] |
[
0.9150390625,
0.0726318359375,
0.0032749176025390625,
0.00909423828125
] |
The rate of freedom from valve-related reintervention was 94% in Groups 1a and 2a after 5 years. Six patients had reintervention in Group 1a vs. three patients in Group 2a. At 5 years, 92% of the patients in Group 1b and 98% of the patients in Group 2b were free from reintervention . Reintervention occurred in seven patients in Group 1b vs. four patients in Group 2b. Reintervention was performed surgically in 16 patients and transcatheter aortic valve replacement was performed in 4 cases. The causes of reinterventions were infective endocarditis (n = 4), degenerated prosthesis (n = 11), paravalvular leak (n = 3), and patient-prosthesis mismatch (n = 2).
|
[
"Fatimah A. Alhijab",
"Latifa A. Alfayez",
"Essam Hassan",
"Monirah A. Albabtain",
"Ismail M. Elnaggar",
"Khaled A. Alotaibi",
"Adam I. Adam",
"Claudio Pragliola",
"Huda H. Ismail",
"Amr A. Arafat"
] |
https://doi.org/10.3390/jcdd11070227
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
39057647_p18
|
39057647
|
sec[2]/sec[5]/p[0]
|
3.6. Freedom from Stroke
| 3.691406 |
biomedical
|
Study
|
[
0.744140625,
0.25341796875,
0.002475738525390625
] |
[
0.876953125,
0.10943603515625,
0.0024585723876953125,
0.01097869873046875
] |
There were five strokes in Group 1a and one stroke in Group 2a. The prevalence of freedom stroke was 87% at 10 years in Group 1a and 94% in Group 2a. Stroke occurred in one patient in Group 1b and two in Group 2b. In both groups, the rate of freedom from stroke was 98% at 10 years .
|
[
"Fatimah A. Alhijab",
"Latifa A. Alfayez",
"Essam Hassan",
"Monirah A. Albabtain",
"Ismail M. Elnaggar",
"Khaled A. Alotaibi",
"Adam I. Adam",
"Claudio Pragliola",
"Huda H. Ismail",
"Amr A. Arafat"
] |
https://doi.org/10.3390/jcdd11070227
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
39057647_p19
|
39057647
|
sec[2]/sec[6]/p[0]
|
3.7. Freedom from Bleeding
| 3.490234 |
biomedical
|
Study
|
[
0.6142578125,
0.382080078125,
0.0034580230712890625
] |
[
0.8056640625,
0.17236328125,
0.0029239654541015625,
0.01885986328125
] |
There were seven bleeding episodes in Group 1a and 3 in Group 2a. There was 85% freedom from bleeding at 10 years in Group 1a and 77% in Group 2a. Four bleeding episodes occurred in Group 1b, and 12 occurred in Group 2b. The rate of freedom from bleeding was 86% at 10 years in both groups .
|
[
"Fatimah A. Alhijab",
"Latifa A. Alfayez",
"Essam Hassan",
"Monirah A. Albabtain",
"Ismail M. Elnaggar",
"Khaled A. Alotaibi",
"Adam I. Adam",
"Claudio Pragliola",
"Huda H. Ismail",
"Amr A. Arafat"
] |
https://doi.org/10.3390/jcdd11070227
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
39057647_p20
|
39057647
|
sec[2]/sec[7]/p[0]
|
3.8. Changes in Echocardiography
| 4.171875 |
biomedical
|
Study
|
[
0.99755859375,
0.0020580291748046875,
0.0002720355987548828
] |
[
0.99853515625,
0.0007410049438476562,
0.0005831718444824219,
0.0001785755157470703
] |
There was a significant reduction in the LV mass in Groups 1a and 2a over follow-up (β: −0.47 (95% CI: −0.60–−0.34), p < 0.001), with no difference between them (β: −6.86 (95% CI: −18.58–4.87), p = 0.252). The changes in ejection fraction were not significant (β: 0.02 (95% CI: −0.003–0.05), p = 0.08), and there was no difference between the groups (β: 2.66 (95% CI: −0.20–5.52), p = 0.068). The peak AV pressure significantly reduced during follow-up (β: −0.51 (95% CI: −0.66–−0.37), p < 0.001), with no difference between Groups 1a and 2a (β: −0.93 (95% CI: −8.23–6.36), p = 0.802) .
|
[
"Fatimah A. Alhijab",
"Latifa A. Alfayez",
"Essam Hassan",
"Monirah A. Albabtain",
"Ismail M. Elnaggar",
"Khaled A. Alotaibi",
"Adam I. Adam",
"Claudio Pragliola",
"Huda H. Ismail",
"Amr A. Arafat"
] |
https://doi.org/10.3390/jcdd11070227
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
39057647_p21
|
39057647
|
sec[2]/sec[7]/p[1]
|
3.8. Changes in Echocardiography
| 4.195313 |
biomedical
|
Study
|
[
0.998046875,
0.0015726089477539062,
0.0002532005310058594
] |
[
0.99853515625,
0.0007028579711914062,
0.00048828125,
0.00015819072723388672
] |
Left ventricular mass decreased significantly over time (β: −0.72 (95% CI: −0.99–−0.44), p < 0.001), with no difference between Groups 1b and 2b (β: 2.39 (95% CI: −9.27–14.04), p = 0.688). There was a significant improvement in EF over time (β: 0.05 (95% CI: 0.02–0.08), p < 0.001), while there was no difference between Groups 1b and 2b (β: −0.73 (95% CI: −3.41–1.97), p = 0.597). There was a reduction in the peak AV pressure, but it did not reach a significant level (β: −0.15 (95% CI: −0.31–0.004), p = 0.056), and there was no difference between Groups 1b and 2b (β: −6.80 (95% CI: −14.58–0.98), p = 0.087) .
|
[
"Fatimah A. Alhijab",
"Latifa A. Alfayez",
"Essam Hassan",
"Monirah A. Albabtain",
"Ismail M. Elnaggar",
"Khaled A. Alotaibi",
"Adam I. Adam",
"Claudio Pragliola",
"Huda H. Ismail",
"Amr A. Arafat"
] |
https://doi.org/10.3390/jcdd11070227
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
39057647_p22
|
39057647
|
sec[3]/p[0]
|
4. Discussion
| 4.113281 |
biomedical
|
Study
|
[
0.98876953125,
0.0107269287109375,
0.00038552284240722656
] |
[
0.9951171875,
0.00232696533203125,
0.001918792724609375,
0.0007109642028808594
] |
The challenges of choosing an aortic valve prosthesis are continuously debated. This study explored the differences in short- and long-term outcomes after AVR between patients who received bioprosthetic and those who received mechanical valves stratified by age. There was no difference in postoperative complications between groups apart from greater re-exploration for bleeding in patients > 50 years old with mechanical valves. The groups had no differences in survival, stroke, or bleeding rates. Aortic valve reintervention was significantly greater in patients ≤ 50 with bioprosthetic valves. There were no differences between groups in the changes in left ventricular mass, ejection fraction, or peak aortic valve pressure during the 5-year follow-up.
|
[
"Fatimah A. Alhijab",
"Latifa A. Alfayez",
"Essam Hassan",
"Monirah A. Albabtain",
"Ismail M. Elnaggar",
"Khaled A. Alotaibi",
"Adam I. Adam",
"Claudio Pragliola",
"Huda H. Ismail",
"Amr A. Arafat"
] |
https://doi.org/10.3390/jcdd11070227
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
39057647_p23
|
39057647
|
sec[3]/p[1]
|
4. Discussion
| 4.148438 |
biomedical
|
Study
|
[
0.998046875,
0.001895904541015625,
0.00028586387634277344
] |
[
0.99853515625,
0.0004940032958984375,
0.0009245872497558594,
0.00015795230865478516
] |
Male patients constituted the vast majority of the participants in all groups; however, the proportion of males was lower in patients ≤ 50 years of age who received bioprosthetic valves. This finding could be attributed to the increased use of bioprosthetic valves in women of childbearing age . A meta-analysis conducted by Grashuis and colleagues showed that bioprosthetic valves for females of childbearing age with plans for future pregnancies were preferred over mechanical valves even when considering the possibility of receiving safe continuous low-dose oral anticoagulation during pregnancy . In this study, the rate of preoperative comorbidities did not vary between the groups except for the rates of hypertension and old stroke, which were greater in patients ≤ 50 years old and who underwent bioprosthetic AVR. This finding could be attributed to the tendency to avoid the risk of anticoagulation in those patients. There were no differences in hospital complications among groups; however, re-exploration for bleeding was higher in older patients with mechanical valves. Not all patients with bioprosthetic valves had warfarin postoperatively, which could explain the higher bleeding rate in older patients with mechanical valves.
|
[
"Fatimah A. Alhijab",
"Latifa A. Alfayez",
"Essam Hassan",
"Monirah A. Albabtain",
"Ismail M. Elnaggar",
"Khaled A. Alotaibi",
"Adam I. Adam",
"Claudio Pragliola",
"Huda H. Ismail",
"Amr A. Arafat"
] |
https://doi.org/10.3390/jcdd11070227
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
39057647_p24
|
39057647
|
sec[3]/p[2]
|
4. Discussion
| 4.15625 |
biomedical
|
Study
|
[
0.99853515625,
0.0012302398681640625,
0.0002205371856689453
] |
[
0.98876953125,
0.0008130073547363281,
0.01030731201171875,
0.0002846717834472656
] |
The long-term use of aortic valve bioprostheses at a young age is controversial. Malvindi and colleagues conducted research comparing bioprosthetic and mechanical AVR in patients between 50 and 69 years old. They reported similar survival, greater bleeding with mechanical valves, and greater reintervention with bioprosthetic valves . Chiang and colleagues reported a greater cumulative incidence of bleeding following mechanical valve replacement than following bioprosthetic valve replacement in patients aged 50–69 years, with greater reintervention with bioprosthetic valves and similar survival and stroke rates . Traxler and associates compared the long-term outcomes of patients aged between 50 and 69 years with bioprosthetic and mechanical valves. They reported a lower risk of bleeding, better survival, and a lower risk of myocardial infarction in patients with mechanical valves . On the other hand, the risk of stroke was similar between the two valves. Kyto and colleagues matched patients with mechanical and bioprosthetic valves aged 50 to 70. They reported lower mortality, reoperation, and infective endocarditis in patients with mechanical valves . Zhao and colleagues performed a meta-analysis of studies comparing mechanical and bioprosthetic AVR in patients aged >50 years . They reported similar survival rates but reduced bleeding and greater structural valve deterioration with bioprosthetic valves. These studies indicate that expanding the indications for bioprosthetic valves in patients aged >50 years should be performed with caution. The risk of reoperation is still high; however, the advancement of transcatheter aortic valve replacement has mitigated the risk of surgical reoperation . Our study demonstrated comparable reintervention and survival rates between both prostheses in patients > 50 years; moreover, there was no increased risk of bleeding or stroke in patients with mechanical valves.
|
[
"Fatimah A. Alhijab",
"Latifa A. Alfayez",
"Essam Hassan",
"Monirah A. Albabtain",
"Ismail M. Elnaggar",
"Khaled A. Alotaibi",
"Adam I. Adam",
"Claudio Pragliola",
"Huda H. Ismail",
"Amr A. Arafat"
] |
https://doi.org/10.3390/jcdd11070227
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
39057647_p25
|
39057647
|
sec[3]/p[3]
|
4. Discussion
| 4.042969 |
biomedical
|
Study
|
[
0.99951171875,
0.0004467964172363281,
0.00018513202667236328
] |
[
0.994140625,
0.00037217140197753906,
0.00518798828125,
0.0001308917999267578
] |
Few studies have reported data on aortic valve prostheses in patients ≤ 50 years. Hirji and colleagues reported comparable mid-term and long-term bleeding and survival in patients with mechanical and bioprosthetic AVR aged 50 years and younger; however, the risk of reoperation was greater with bioprosthetic valves . Similar findings were reported in other studies . A study by Corona and colleagues reported similar structural bioprosthetic aortic valve deterioration in young and old patients . Our study reported comparable survival, bleeding, and stroke rates in patients aged 50 years and younger; however, aortic valve reintervention remains an issue with bioprosthetic valves.
|
[
"Fatimah A. Alhijab",
"Latifa A. Alfayez",
"Essam Hassan",
"Monirah A. Albabtain",
"Ismail M. Elnaggar",
"Khaled A. Alotaibi",
"Adam I. Adam",
"Claudio Pragliola",
"Huda H. Ismail",
"Amr A. Arafat"
] |
https://doi.org/10.3390/jcdd11070227
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
39057647_p26
|
39057647
|
sec[3]/p[4]
|
4. Discussion
| 3.980469 |
biomedical
|
Study
|
[
0.998046875,
0.001903533935546875,
0.00018417835235595703
] |
[
0.9921875,
0.0042877197265625,
0.00287628173828125,
0.0005464553833007812
] |
In summary, our study demonstrated that bioprosthetic and mechanical valves could be viable options for patients older than 50 years; however, bioprosthetic valves should be used with caution in younger patients because of the greater risk of reintervention.
|
[
"Fatimah A. Alhijab",
"Latifa A. Alfayez",
"Essam Hassan",
"Monirah A. Albabtain",
"Ismail M. Elnaggar",
"Khaled A. Alotaibi",
"Adam I. Adam",
"Claudio Pragliola",
"Huda H. Ismail",
"Amr A. Arafat"
] |
https://doi.org/10.3390/jcdd11070227
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
39057647_p27
|
39057647
|
sec[3]/sec[0]/p[0]
|
Study Limitations
| 4.082031 |
biomedical
|
Study
|
[
0.9990234375,
0.0008573532104492188,
0.00018906593322753906
] |
[
0.9990234375,
0.0003840923309326172,
0.0006833076477050781,
0.00014495849609375
] |
This study has limitations. First, the sample size was relatively small, with an uneven distribution across the different groups. These differences could be attributed to the current recommendations for aortic valve prostheses. Second, this was a single-center study, and using anticoagulation protocols and follow-up could affect the outcomes. Third, the study is retrospective, with inherent referral and selection biases. Fourth, the valve type could have affected the outcomes, which were not evaluated in this study. Finally, the long-term follow-up is limited. Most reinterventions for bioprosthetic valve degeneration occur after 10 years and not all patients in our study completed 10 years. Studies with longer follow-ups beyond 10 years are recommended.
|
[
"Fatimah A. Alhijab",
"Latifa A. Alfayez",
"Essam Hassan",
"Monirah A. Albabtain",
"Ismail M. Elnaggar",
"Khaled A. Alotaibi",
"Adam I. Adam",
"Claudio Pragliola",
"Huda H. Ismail",
"Amr A. Arafat"
] |
https://doi.org/10.3390/jcdd11070227
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
39057647_p28
|
39057647
|
sec[4]/p[0]
|
5. Conclusions
| 3.962891 |
biomedical
|
Review
|
[
0.9970703125,
0.00254058837890625,
0.0004875659942626953
] |
[
0.44287109375,
0.0180816650390625,
0.53759765625,
0.0013570785522460938
] |
Aortic valve replacement can be performed safely in adult patients using both biological and prosthetic valves, as they showed similar early survival rates. The outcomes of mechanical and bioprosthetic valves were comparable in patients older than 50 years. Using bioprosthetic valves in patients younger than 50 years was associated with a greater rate of valve reintervention, with no beneficial effect on the risk of bleeding or stroke.
|
[
"Fatimah A. Alhijab",
"Latifa A. Alfayez",
"Essam Hassan",
"Monirah A. Albabtain",
"Ismail M. Elnaggar",
"Khaled A. Alotaibi",
"Adam I. Adam",
"Claudio Pragliola",
"Huda H. Ismail",
"Amr A. Arafat"
] |
https://doi.org/10.3390/jcdd11070227
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277730_p0
|
PMC11277730
|
sec[0]/sec[0]/p[0]
|
1.1. Photocarcinogenesis
| 4.027344 |
biomedical
|
Other
|
[
0.9990234375,
0.00043201446533203125,
0.0004138946533203125
] |
[
0.336669921875,
0.44921875,
0.2122802734375,
0.0017099380493164062
] |
Photocarcinogenesis is a complex process where ultraviolet (UV) radiation from sunlight contributes to skin cancer development through various molecular mechanisms . UV radiation (UVR) includes the UVA, UVB, and UVC bands, with UVA and UVB being the most significant in sunlight exposure. These radiation types penetrate the skin, inducing DNA damage directly or indirectly, leading to mutations that can result in skin cancer .
|
[
"Emilio Garcia-Mouronte",
"Luis Alfonso Pérez-González",
"Jorge Naharro-Rodriguez",
"Montserrat Fernández Guarino"
] |
https://doi.org/10.3390/life14070822
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11277730_p1
|
PMC11277730
|
sec[0]/sec[0]/p[1]
|
1.1. Photocarcinogenesis
| 4.898438 |
biomedical
|
Review
|
[
0.9951171875,
0.0024814605712890625,
0.0021724700927734375
] |
[
0.197998046875,
0.003662109375,
0.796875,
0.0014171600341796875
] |
UVR increases the production of reactive oxygen species (ROS), which can damage DNA, proteins, and lipids in skin cells, contributing to carcinogenesis . The interaction between UV light and the skin activates specific signaling pathways that lead to DNA mutations . Prolonged UV exposure can cause chronic inflammation, which promotes tumor growth and invasion by acting in the tumor microenvironment, promoting angiogenesis, and suppressing the immune response to tumor cells . Key molecular players in photocarcinogenesis include the p53 protein, a tumor suppressor gene that plays the main role in controlling cell cycle arrest and apoptosis in response to DNA damage . UV-induced mutations in the p53 gene are common in skin cancers, leading to the loss of function of this critical protein, allowing uncontrolled cell division . Another mechanism involves the activation of the MAP kinase pathways, which influences cell proliferation and survival, further contributing to the development of skin cancer . Additionally, the upregulation of RAS oncogenes and the inactivation of tumor suppressor genes, as PTEN, are also pivotal in the development of skin cancer following UV exposure . These genetic changes accumulate over time, increasing the risk of malignant transformation of skin cells . Research continues to uncover the detailed molecular pathways involved in photocarcinogenesis, offering potential targets for prevention and treatment strategies .
|
[
"Emilio Garcia-Mouronte",
"Luis Alfonso Pérez-González",
"Jorge Naharro-Rodriguez",
"Montserrat Fernández Guarino"
] |
https://doi.org/10.3390/life14070822
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277730_p2
|
PMC11277730
|
sec[0]/sec[1]/p[0]
|
1.2. Photoaging and Hyperpigmentation
| 4.328125 |
biomedical
|
Review
|
[
0.99609375,
0.0018968582153320312,
0.0021152496337890625
] |
[
0.0192108154296875,
0.01032257080078125,
0.9697265625,
0.0007448196411132812
] |
Photoaging is characterized by deep wrinkles, hyperpigmentation, and loss of skin elasticity and results from chronic exposure to UV . Both UVA and UVB damage the skin through the generation of ROS, which disrupt DNA and degrade collagen, accelerating the aging process . UVA rays penetrate deeper into the dermis, exacerbating photoaging by breaking down collagen and elastin, the fibers that support skin structure . UVB rays, though primarily affecting the epidermis, also contribute significantly to photoaging by promoting the formation of wrinkles and increasing epidermal disorganization, thickness, and roughness . The oxidative stress from UV exposure leads to the inflammation and degradation of collagen and elastic fibers, which are essential for maintaining skin’s youthful appearance . Preventive measures against photoaging include the application of broad-spectrum sunscreens (SC) that protect against both UVA and UVB . Modern formulations often include antioxidants and other additives that not only protect against but may also reverse some signs of aging .
|
[
"Emilio Garcia-Mouronte",
"Luis Alfonso Pérez-González",
"Jorge Naharro-Rodriguez",
"Montserrat Fernández Guarino"
] |
https://doi.org/10.3390/life14070822
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999999 |
PMC11277730_p3
|
PMC11277730
|
sec[0]/sec[1]/p[1]
|
1.2. Photoaging and Hyperpigmentation
| 3.998047 |
biomedical
|
Study
|
[
0.9990234375,
0.00016987323760986328,
0.0006918907165527344
] |
[
0.9345703125,
0.0025882720947265625,
0.0628662109375,
0.00020599365234375
] |
Industrialization, digitalization, and the fast-growing use of electronic devices such as mobile phones, laptops, and tablets haved had a significant impact on daily lifestyle, with increased and continuous exposure to artifical light sources, including blue light . In vitro studies have shown blue light exposure leads to DNA damage, oxidative stress alteration of collagen and elastin, reduced immunosurveillance, and increased apoptosis . A dose-dependent influence has been suggested . Additionally, what is clearly demonstrated among studies of blue light on the skin is the induction of hyperpigmentation .
|
[
"Emilio Garcia-Mouronte",
"Luis Alfonso Pérez-González",
"Jorge Naharro-Rodriguez",
"Montserrat Fernández Guarino"
] |
https://doi.org/10.3390/life14070822
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277730_p4
|
PMC11277730
|
sec[0]/sec[1]/p[2]
|
1.2. Photoaging and Hyperpigmentation
| 3.269531 |
biomedical
|
Other
|
[
0.9931640625,
0.0003674030303955078,
0.00644683837890625
] |
[
0.25244140625,
0.74072265625,
0.00647735595703125,
0.0004780292510986328
] |
Thus, the recognition that visible light (VL) and infrared radiation contribute to photoaging suggests the need for SCs that cover a broader spectrum of light . The use of tinted SCs, which combine physical blockers like zinc oxide and titanium dioxide with iron oxides, can protect against the full spectrum of light contributing to photoaging .
|
[
"Emilio Garcia-Mouronte",
"Luis Alfonso Pérez-González",
"Jorge Naharro-Rodriguez",
"Montserrat Fernández Guarino"
] |
https://doi.org/10.3390/life14070822
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11277730_p5
|
PMC11277730
|
sec[0]/sec[1]/p[3]
|
1.2. Photoaging and Hyperpigmentation
| 3.931641 |
biomedical
|
Other
|
[
0.99853515625,
0.0005459785461425781,
0.0009303092956542969
] |
[
0.1337890625,
0.517578125,
0.346923828125,
0.0015192031860351562
] |
Photoprotection is essential for safeguarding the skin from the harmful effects of electromagnetic radiation, particularly UV and VL . There are various types of photoprotection strategies available . These include physical measures such as wearing photoprotective clothing, seeking shade, and using broad-spectrum SC . Broad-spectrum SCs are critical as they provide protection against both UVA and UVB rays, the main contributors to skin damage . In terms of SC composition, there are both organic and inorganic filters . Moreover, tinted SCs provide an additional layer of protection against VL, which can contribute to photoaging and hyperpigmented conditions like melasma .
|
[
"Emilio Garcia-Mouronte",
"Luis Alfonso Pérez-González",
"Jorge Naharro-Rodriguez",
"Montserrat Fernández Guarino"
] |
https://doi.org/10.3390/life14070822
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11277730_p6
|
PMC11277730
|
sec[0]/sec[2]/p[0]
|
1.3. Active Photoprotection
| 3.169922 |
biomedical
|
Other
|
[
0.9951171875,
0.00101470947265625,
0.0037097930908203125
] |
[
0.0175018310546875,
0.90087890625,
0.08062744140625,
0.0008955001831054688
] |
Photoprotection encompasses a wide set of behavioral, physical, and chemical measures aiming at preventing or limiting the acute and chronic deleterious effects of UVR on human skin . Although avoidance of sun exposure is by far the most effective photostrategy, its real-life application is extremely challenging and often impracticable, especially in outdoor workplaces and regions with high solar radiation .
|
[
"Emilio Garcia-Mouronte",
"Luis Alfonso Pérez-González",
"Jorge Naharro-Rodriguez",
"Montserrat Fernández Guarino"
] |
https://doi.org/10.3390/life14070822
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277730_p7
|
PMC11277730
|
sec[0]/sec[2]/p[1]
|
1.3. Active Photoprotection
| 2.269531 |
biomedical
|
Other
|
[
0.98974609375,
0.0008187294006347656,
0.0092620849609375
] |
[
0.0217437744140625,
0.96923828125,
0.008148193359375,
0.0007500648498535156
] |
SCs are composed of mineral and organic compounds (filters) capable of scattering and neutralizing different wavelengths, including UVR and VL . Due to their ease of application, continuous pharmacological innovation, and consciousness-raising awareness, their use has become widespread in numerous geographic areas during the last several decades .
|
[
"Emilio Garcia-Mouronte",
"Luis Alfonso Pérez-González",
"Jorge Naharro-Rodriguez",
"Montserrat Fernández Guarino"
] |
https://doi.org/10.3390/life14070822
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277730_p8
|
PMC11277730
|
sec[0]/sec[2]/p[2]
|
1.3. Active Photoprotection
| 4.0625 |
biomedical
|
Review
|
[
0.994140625,
0.0020313262939453125,
0.00368499755859375
] |
[
0.0164794921875,
0.0010271072387695312,
0.982421875,
0.00023686885833740234
] |
Depending on their mechanism of action, SCs can be subdivided into “passive” and “active” . Passive photoprotection, which is the traditional and most frequently employed approach, consists in the topical use of filters that reflect UVR and VL . Despite their mechanism of action, they can indeed be overcome by inflicting radiation, especially when inappropriately applied . Furthermore, filters are ineffective in reverting skin damage induced by UVR and VL once it has happened . To fill this gap, chemical compounds have been extensively researched to limit the oxidative insult and DNA damage after sun exposure, which are collectively known as “active photoprotection” . Most of these substances are naturally occurring molecules extracted from plants and algae . Despite their recent development and increasing use, scientific reviews assessing the efficacy and safety of active photoprotective agents as a whole are lacking in the available literature. Available reviews on this topic are scarce, are mostly focused on a certain subset of agents, and consist mainly of preclinical or animal studies .
|
[
"Emilio Garcia-Mouronte",
"Luis Alfonso Pérez-González",
"Jorge Naharro-Rodriguez",
"Montserrat Fernández Guarino"
] |
https://doi.org/10.3390/life14070822
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11277730_p9
|
PMC11277730
|
sec[0]/sec[2]/p[3]
|
1.3. Active Photoprotection
| 3.931641 |
biomedical
|
Review
|
[
0.99560546875,
0.001689910888671875,
0.002716064453125
] |
[
0.01126861572265625,
0.00333404541015625,
0.98486328125,
0.0004031658172607422
] |
For these reasons, the aim of this work is reviewing the state-of-the-art in active photoprotection by thoroughly assessing the current scientific available data on the use of antioxidant substances and DNA-repair enzymes in human skin, especially in in vivo models and clinical trials.
|
[
"Emilio Garcia-Mouronte",
"Luis Alfonso Pérez-González",
"Jorge Naharro-Rodriguez",
"Montserrat Fernández Guarino"
] |
https://doi.org/10.3390/life14070822
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277730_p10
|
PMC11277730
|
sec[1]/sec[0]/sec[0]/p[0]
|
2.1.1. Evolutionary Origin and Mechanism of Action
| 4.175781 |
biomedical
|
Study
|
[
0.99951171875,
0.0002689361572265625,
0.00020182132720947266
] |
[
0.93896484375,
0.0171966552734375,
0.04351806640625,
0.0005054473876953125
] |
UV exposure may result in notable deleterious effects on human skin cells. Although single and double strand-breaks can occur, most changes in chromosomal DNA consist of chemical modifications of nitrogenous bases, especially cyclobutane pyrimidine dimers (CPD) and pyrimidine (6-4) pyrimidone photoproducts (6-4PP) . When interfering with key cellular processes such as replication and transcription, they lead to cell cycle arrest and ultimately apoptosis . Conversely, if DNA damage is persistent, numerous gene mutations can build up, allowing cells to escape from controlled growth and increasing the risk of malignant transformation .
|
[
"Emilio Garcia-Mouronte",
"Luis Alfonso Pérez-González",
"Jorge Naharro-Rodriguez",
"Montserrat Fernández Guarino"
] |
https://doi.org/10.3390/life14070822
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11277730_p11
|
PMC11277730
|
sec[1]/sec[0]/sec[0]/p[1]
|
2.1.1. Evolutionary Origin and Mechanism of Action
| 4.164063 |
biomedical
|
Study
|
[
0.99951171875,
0.00018727779388427734,
0.0004296302795410156
] |
[
0.96875,
0.0190582275390625,
0.011993408203125,
0.0002434253692626953
] |
For these reasons, organisms have developed during the course of time a complex network of repair mechanisms with different but complementary substrates, which keep DNA under constant monitoring . The removal of photolesions is mostly conducted by the highly evolutionary conserved nucleotide excision repair (NER) pathway . While this system rapidly corrects common photoproducts, such as 6-4PPs, its effects on CPD are far more modest .
|
[
"Emilio Garcia-Mouronte",
"Luis Alfonso Pérez-González",
"Jorge Naharro-Rodriguez",
"Montserrat Fernández Guarino"
] |
https://doi.org/10.3390/life14070822
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277730_p12
|
PMC11277730
|
sec[1]/sec[0]/sec[0]/p[2]
|
2.1.1. Evolutionary Origin and Mechanism of Action
| 4.464844 |
biomedical
|
Study
|
[
0.99951171875,
0.00027251243591308594,
0.0003426074981689453
] |
[
0.927734375,
0.0024623870849609375,
0.06939697265625,
0.0003631114959716797
] |
A wide array of organisms found in the archaea, bacteria, and eukarya domains have mounted an additional DNA-repair mechanism known as photoreactivation, firstly described by Kelner in 1949 . This is based on photolyases, flavoprotein-based monomeric enzymes that repair damaged ssDNA and dsDNA using blue wavelength as an energy source . Compared to NER, the biochemical mechanism is more simple and consists of the rapid cleavage of photoproducts into their original undamaged state, thanks to electron transfers from the photo-excited flavin to the dimer . Interestingly, photolyases show marked substrate specificity and are subdivided into CPD photolyases and 6-4PP photolyases .
|
[
"Emilio Garcia-Mouronte",
"Luis Alfonso Pérez-González",
"Jorge Naharro-Rodriguez",
"Montserrat Fernández Guarino"
] |
https://doi.org/10.3390/life14070822
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11277730_p13
|
PMC11277730
|
sec[1]/sec[0]/sec[0]/p[3]
|
2.1.1. Evolutionary Origin and Mechanism of Action
| 4.191406 |
biomedical
|
Study
|
[
0.99951171875,
0.00015354156494140625,
0.0004582405090332031
] |
[
0.9853515625,
0.0017251968383789062,
0.01291656494140625,
0.00013303756713867188
] |
Nevertheless, placental mammals, including humans, are strictly dependent on the NER pathway to repair UV-induced DNA damage . According to the “nocturnal bottleneck hypothesis” conjectured by Menaker et al. , early eutherian mammals were small night-active insectivores living on trees . Arising in the Mesozoic era after the Permian–Triassic event, they were forced to live in light-restricted environments as they faced inter-species competition and predation pressure by diurnal dinosaurs . These factors led to significant changes in their homeostasis, such as the evolution of endothermia, the loss of underused photoreceptor structures and certain photoprotective mechanisms such as photolyases in light-exposed tissues .
|
[
"Emilio Garcia-Mouronte",
"Luis Alfonso Pérez-González",
"Jorge Naharro-Rodriguez",
"Montserrat Fernández Guarino"
] |
https://doi.org/10.3390/life14070822
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11277730_p14
|
PMC11277730
|
sec[1]/sec[0]/sec[1]/p[0]
|
2.1.2. Scientific Evidence: General Overview
| 3.953125 |
biomedical
|
Review
|
[
0.998046875,
0.00115203857421875,
0.0010013580322265625
] |
[
0.2401123046875,
0.0010652542114257812,
0.75830078125,
0.00043964385986328125
] |
The use of topical photolyases (TPHs) as active SCs is overwhelmingly supported by current data . Since 2000, four randomized control trials (RCTs) , one experimental trial , five pilot interventional studies , one longitudinal observational clinical trial , and five observational studies have been published that underline the efficacy of TPHs in the management of actinic keratoses (AKs) (n = 12) , but also in additional disorders such as xeroderma pigmentosum (XP) , polymorphic light eruption (PoLE) , and in the general population . In almost a half of these works (n = 7), the use of TPHs was compared against regular SPF30-50+ SC . Although the follow-up periods were heterogeneous (3 days –1 year ), most of the studies (n = 9) were long enough (≥3 months) to validly assess the clearance of AK lesions.
|
[
"Emilio Garcia-Mouronte",
"Luis Alfonso Pérez-González",
"Jorge Naharro-Rodriguez",
"Montserrat Fernández Guarino"
] |
https://doi.org/10.3390/life14070822
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277730_p15
|
PMC11277730
|
sec[1]/sec[0]/sec[1]/p[1]
|
2.1.2. Scientific Evidence: General Overview
| 3.701172 |
biomedical
|
Study
|
[
0.9990234375,
0.0001685619354248047,
0.000614166259765625
] |
[
0.5478515625,
0.0570068359375,
0.39453125,
0.0006322860717773438
] |
Different and complex methods have been employed to study in vivo the effects of TPHs on human skin, including clinical scores (AKASI, AKSS, FPS) , non-invasive diagnostic techniques such as dermoscopy , reflectance confocal microscopy (RCM) , fluorescence , colorimetry , telethermography , biopsies , and RNA extraction .
|
[
"Emilio Garcia-Mouronte",
"Luis Alfonso Pérez-González",
"Jorge Naharro-Rodriguez",
"Montserrat Fernández Guarino"
] |
https://doi.org/10.3390/life14070822
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11277730_p16
|
PMC11277730
|
sec[1]/sec[0]/sec[1]/p[2]
|
2.1.2. Scientific Evidence: General Overview
| 4.011719 |
biomedical
|
Study
|
[
0.99951171875,
0.00023090839385986328,
0.0002053976058959961
] |
[
0.99755859375,
0.0010890960693359375,
0.00116729736328125,
0.00008493661880493164
] |
Regarding the source of TPHs, all authors conducted their investigations with photolyases (0.5–1%) extracted from the blue–green algae Anacystis nidulans and encapsulated in liposomes . These are mostly commercialized under the mark Eryfotona AK-NMSC fluid ® (Isdin, Barcelona, Spain), which is a film-forming medical broad-spectrum SPF100+ SC. In two works , patients were simultaneously treated with topical endonucleases (0.5–1%) derived from the bacterium Micrococcus luteus . Most were combined with broad-spectrum SPF50+ SC . Depending on the clinical indication, the TPHs were applied 30 min before UVR , 5 –60 min post–UVR, once or twice daily .
|
[
"Emilio Garcia-Mouronte",
"Luis Alfonso Pérez-González",
"Jorge Naharro-Rodriguez",
"Montserrat Fernández Guarino"
] |
https://doi.org/10.3390/life14070822
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277730_p17
|
PMC11277730
|
sec[1]/sec[0]/sec[2]/p[0]
|
2.1.3. In Vivo Pilot Experimental Trials
| 4.289063 |
biomedical
|
Study
|
[
0.99951171875,
0.00039887428283691406,
0.00022459030151367188
] |
[
0.9990234375,
0.0002338886260986328,
0.0007686614990234375,
0.00009107589721679688
] |
The first in vivo experimental trial that confirmed the reduction of CPD levels in human skin by TPHs was published by Stege et al. in 2000 ( Table 1 ). Buttock sites (area = 16 cm 2 ) of 19 healthy participants with low phototypes (II–III) were exposed to UVB radiation (1–2 minimal erythema doses (MEDs)) and treated afterwards with a hydrogel containing Anacystis nidulans 1% encapsulated in liposomes . Differently from commercialized products, the hydrogel lacked filters, which allowed the authors to assess the effects of TPHs on irradiated human cells, avoiding the synergistic influence of SC . The photoactivation of TPH was achieved using blue light (λ = 340–450 nm) for 30 min . Biopsies were taken immediately after and 1 day after UV exposure . CPD levels were assessed by fluorescence . UVB (1 MED) significantly increased the presence of CPD in human cells compared to sham-irradiated sites (97 au vs. 10 au) . After photoactivation, TPH rapidly reduced the levels of CPD in a time-dependent manner (1 min: 100 au, 5 min: 87 au, 30 min: 60 au, −42%). The repair effect was at its maximum level just after the completion of photoactivation, since the amount of CPD did not change 24 h after TPH administration (−44%). The authors also investigated whether TPH could partially revert UV-induced immunosuppression . The expression of ICAM-1, a protein vital for eliciting cellular immune responses, was assessed before and after the subcutaneous administration of IFN-γ through fluorescence. ICAM-1 levels in sham-irradiated areas and UV-radiated did not change after IFN-γ administration (10 au vs. 8 au and 52 vs. 55 au, respectively) . TPH managed to partially decrease its expression after IFN-γ injection and photoactivation (29 au) .
|
[
"Emilio Garcia-Mouronte",
"Luis Alfonso Pérez-González",
"Jorge Naharro-Rodriguez",
"Montserrat Fernández Guarino"
] |
https://doi.org/10.3390/life14070822
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11277730_p18
|
PMC11277730
|
sec[1]/sec[0]/sec[2]/p[1]
|
2.1.3. In Vivo Pilot Experimental Trials
| 4.265625 |
biomedical
|
Study
|
[
0.99658203125,
0.003192901611328125,
0.00027489662170410156
] |
[
0.99609375,
0.0025482177734375,
0.0007119178771972656,
0.00041604042053222656
] |
Eleven years later, Berardesca et al. published the results of a pilot interventional clinical study comparing for the first time the use of TPHs combined with broad-spectrum SPF50+ SC to SC alone ( Table 1 ) . Ten healthy young individuals with FFII were recruited . Five experimental sites from unspecified anatomical locations were used as the control (n = 1) and exposed to ssUVR, ssUVR + Vehicle, ssUVR + SC and ssUVR + TPH + SC . ssUVR (λ = 290–400 nm, 3 MEDs) was administered daily for 4 consecutive days . Topical products were applied once daily, 30 min before each ssUVR . Biopsies were taken from all sites 3 days after the last UV exposure . ELISA was employed for CPD determination . Compared to the baseline, the expression of CPD dramatically increased after ssUVR exposure (x19) and was not mitigated by the application of the vehicle (x19) . TPH + SC significantly reduced the levels of CPD after ssUVR (−93% compared to ssUVR-sites) and were superior to SC alone (−62%, p < 0.001) . However, no treatment managed to revert the amount of CPD in human skin to baseline levels before ssUVR . In addition to preventing the formation of photoproducts, TPH + SC considerably mitigated UVR-induced DNA fragmentation and cellular apoptosis (−82%) and were again superior to SC alone (−40%, p < 0.001) . These results indicated TPHs could be employed as an additional constituent in broad-spectrum SC, palliating the deleterious effects of UVR not appropriately neutralized by filters . Since no treatment fully reverted DNA damage to baseline levels, sun avoidance continues to be the best photoprotective strategy .
|
[
"Emilio Garcia-Mouronte",
"Luis Alfonso Pérez-González",
"Jorge Naharro-Rodriguez",
"Montserrat Fernández Guarino"
] |
https://doi.org/10.3390/life14070822
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
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