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Authors = Arielle Springer

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24 pages, 2607 KiB  
Review
HIF-1α-Mediated Disruption of Cellular Junctions: The Impact of Hypoxia on the Tumor Microenvironment and Invasion
by Michael Springer, Zeynep Aydin Burakgazi, Anastasiia Domukhovska, Ben Nafchi, Michael C. Beary, Arielle Acquisto, Juliette Acquisto, Vladyslav Komarov, Madison Jensen, Brandon Gulledge, Maksym Poplavskyi, Md Gias Uddin, Gamal Rayan and Shoshanna N. Zucker
Int. J. Mol. Sci. 2025, 26(11), 5101; https://doi.org/10.3390/ijms26115101 - 26 May 2025
Viewed by 1047
Abstract
Hypoxia is a critical factor affecting tissue homeostasis that dramatically alters the tumor microenvironment (TME) through genetic, metabolic, and structural changes, promoting tumor survival and proliferation. Hypoxia-inducible factor-1α (HIF-1α) plays a central role in this process by regulating hundreds of genes involved in [...] Read more.
Hypoxia is a critical factor affecting tissue homeostasis that dramatically alters the tumor microenvironment (TME) through genetic, metabolic, and structural changes, promoting tumor survival and proliferation. Hypoxia-inducible factor-1α (HIF-1α) plays a central role in this process by regulating hundreds of genes involved in the processes of tumorigenesis, angiogenesis, metabolic reprogramming, and immune evasion. This review provides a comprehensive examination of the role of HIF-1α in hypoxia and how hypoxia weakens intercellular junctions—including gap junctions, adherens junctions, tight junctions, and desmosomes. The disruption of gap junctions decreases intercellular communication, which alters signal transduction cascades and tumor suppressive properties. Adherens junctions are comprised of proteins that characterize the tissues and link cells to the actin cytoskeleton, whereby their disruption promotes the epithelial-to-mesenchymal transition (EMT). Under hypoxic conditions, the tight junction proteins are dysregulated, altering paracellular transport and cell polarity. In addition, desmosomes provide linkage to intermediate filaments, and hypoxia compromises tissue integrity. Collectively, the influence of hypoxia on cellular junctions promotes tumorigenesis through reducing cell communication, cytoskeletal interactions, and altering signaling pathways. Activation of matrix metalloproteinases (MMPs) further degrades the extracellular matrix and enhances tumor invasion and metastasis. This process also involves hypoxia-induced angiogenesis, regulated by HIF-1α. A comprehensive understanding of the mechanisms of hypoxia-driven tumor adaptation is essential for developing effective therapeutic strategies. Furthermore, this review examines current treatments aimed at targeting HIF-1α and explores future directions to enhance treatment efficacy and improve patient outcomes. Full article
(This article belongs to the Special Issue Molecular Biology of Hypoxia)
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23 pages, 2100 KiB  
Article
Safety Assessment of Recycled Plastics from Post-Consumer Waste with a Combination of a Miniaturized Ames Test and Chromatographic Analysis
by Elisa Mayrhofer, Lukas Prielinger, Victor Sharp, Bernhard Rainer, Christian Kirchnawy, Christian Rung, Anita Gruner, Mladen Juric and Arielle Springer
Recycling 2023, 8(6), 87; https://doi.org/10.3390/recycling8060087 - 4 Nov 2023
Cited by 14 | Viewed by 6908
Abstract
European circular economy goals require the use of recycled polymers in sensitive applications such as food packaging. As plastic recyclates can contain unknown post-consumer substances, the European Food Safety Authority evaluates recycling processes using a worst-case assumption: all contaminants are DNA-reactive mutagens/carcinogens with [...] Read more.
European circular economy goals require the use of recycled polymers in sensitive applications such as food packaging. As plastic recyclates can contain unknown post-consumer substances, the European Food Safety Authority evaluates recycling processes using a worst-case assumption: all contaminants are DNA-reactive mutagens/carcinogens with extremely low safety thresholds. The current data are insufficient to estimate whether this assumption is justified. To provide scientific evidence on the presence of DNA-reactive mutagens in recycled plastics, 119 input and output samples from plastic recycling were tested with a miniaturized Ames test. DNA-reactive mutagens were not detected in recycled polyethylene terephthalate, which is already approved for food contact. However, other types of recycled plastics (polyethylene, polypropylene and polystyrene), which are currently unauthorized for food contact, showed DNA-reactive, mutagenic effects in a total of 51 samples. The DNA-reactive substances that are responsible for the detected mutagenic activity could not be identified by comparison of the bioassay data with analytical results from a chromatographical screening. The data from the Ames test analysis of different independent batches and a comparison of input and output material indicate that the DNA-reactive contaminants are not randomly introduced through the misuse of recycled packaging by consumers, but are systematically formed during the recycling process from precursors in the input. This publication highlights the need to identify the source for this critical contaminant to enable the future use of polyethylene, polypropylene and polystyrene in sensitive applications. Full article
(This article belongs to the Special Issue Advances in the Recycling, Processing and Use of Plastic Waste II)
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23 pages, 4040 KiB  
Article
The Influence of Antioxidant Plant Extracts on the Oxidation of O/W Emulsions
by Arielle Springer, Helena Ziegler and Katrin Bach
Cosmetics 2023, 10(2), 40; https://doi.org/10.3390/cosmetics10020040 - 24 Feb 2023
Cited by 7 | Viewed by 4045
Abstract
The demand for natural cosmetics has steadily increased in recent years. However, challenges occur especially in quality preservation regarding oxidative spoilage of natural cosmetic products, as the use of synthetic preservatives and antioxidants is limited. Therefore, it is important to find nature-based ingredients [...] Read more.
The demand for natural cosmetics has steadily increased in recent years. However, challenges occur especially in quality preservation regarding oxidative spoilage of natural cosmetic products, as the use of synthetic preservatives and antioxidants is limited. Therefore, it is important to find nature-based ingredients to ensure shelf life in natural cosmetic formulations. As a result, potential is seen in the use of plant-based antioxidant extracts. The aim of this work was to determine the suitability of the method combination by measuring the antioxidant activity, oxygen concentration, and volatile oxidation products via gas chromatography (hexanal) for the characterization of the influence of some plant extracts on the oxidative stability of natural cosmetic emulsions. Plant extracts of Riesling (Vitis vinifera) pomace, apple (Malus domestica) pomace, coffee (Coffea arabica) grounds, cocoa (Theobroma cacao) husk, and coffee (Coffea arabica) powder extract were incorporated in stable O/W emulsion formulations, while an emulsion without extract functioned as blank. Afterwards, the emulsions were subjected to 3-month accelerated storage tests with and without light exposure. Their oxygen uptake was investigated, and headspace gas chromatography measurements were performed to detect the fatty acid oxidation products formed during oxidative processes in the samples. The results showed that all emulsion samples under light exposure had a higher oxygen uptake and an increase in the characteristic fatty acid oxidation products compared with those stored under light exclusion. However, differences in oxygen uptake under light exposure were observed depending on the plant extract. Therefore, for O/W emulsions, the daily oxygen consumption rate correlated exponentially with the antioxidant activity, and the hexanal concentration correlated linearly with the daily oxygen consumption rate. Full article
(This article belongs to the Special Issue Feature Papers in Cosmetics in 2022)
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19 pages, 8535 KiB  
Article
Identification and Evaluation of (Non-)Intentionally Added Substances in Post-Consumer Recyclates and Their Toxicological Classification
by Christian Rung, Frank Welle, Anita Gruner, Arielle Springer, Zacharias Steinmetz and Katherine Munoz
Recycling 2023, 8(1), 24; https://doi.org/10.3390/recycling8010024 - 9 Feb 2023
Cited by 27 | Viewed by 8828
Abstract
According to the European circular economy strategy, all plastic packaging placed on the market by 2030 has to be recyclable. However, for recycled plastics in direct contact with food, there are still major safety concerns because (non-)intentionally added substances can potentially migrate from [...] Read more.
According to the European circular economy strategy, all plastic packaging placed on the market by 2030 has to be recyclable. However, for recycled plastics in direct contact with food, there are still major safety concerns because (non-)intentionally added substances can potentially migrate from recycled polymers into foodstuffs. Therefore, the European Food Safety Authority (EFSA) has derived very low migration limits (e.g., 0.1 µg/L for recycled polyethylene terephthalate (PET) and 0.06 µg/L for recycled high-density polyethylene (HDPE)) for recycled polymers. Thus, the use of recyclates from post-consumer waste materials in direct food contact is currently only possible for PET. A first step in assessing potential health hazards is, therefore, the identification and toxicological classification of detected substances. Within this study, samples of post-consumer recyclates from different packaging-relevant recycling materials (HDPE, LDPE, PE, PP, PET, and PS) were analyzed. The detected substances were identified and examined with a focus on their abundance, toxicity (Cramer classification), polarity (log P values), chemical diversity, and origin (post-consumer substances vs. virgin base polymer substances). It was demonstrated that polyolefins contain more substances classified as toxic than PET, potentially due to their higher diffusivity. In addition, despite its low diffusivity compared to polyolefins, a high number of substances was found in PS. Further, post-consumer substances were found to be significantly more toxicologically concerning than virgin base polymer substances. Additionally, a correlation between high log P values and a high Cramer classification was found. It was concluded that PET is currently the only polymer that complies with EFSA’s requirements for a circular economy. However, better-structured collection systems and cleaning processes, as well as more analytical methods that enable a highly sensitive detection and identification of substances, might offer the possibility of implementing other polymers into recycling processes in the future. Full article
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15 pages, 1436 KiB  
Article
Measurement of Stress Relief during Scented Cosmetic Product Application Using a Mood Questionnaire, Stress Hormone Levels and Brain Activation
by Arielle Springer, Laura Höckmeier, Doris Schicker, Stefan Hettwer and Jessica Freiherr
Cosmetics 2022, 9(5), 97; https://doi.org/10.3390/cosmetics9050097 - 15 Sep 2022
Cited by 9 | Viewed by 8118
Abstract
Nowadays, consumers’ well-being plays a decisive role in the purchase of cosmetic products. Although factors influencing consumers’ well-being are very subjective, companies strive to develop their products in such a way that a positive effect is likely. Therefore, methods are required to objectively [...] Read more.
Nowadays, consumers’ well-being plays a decisive role in the purchase of cosmetic products. Although factors influencing consumers’ well-being are very subjective, companies strive to develop their products in such a way that a positive effect is likely. Therefore, methods are required to objectively explore and scientifically prove the product’s performance on humans. In this placebo-controlled study, a method was developed to evaluate relaxation or stress relief associated with one olfactory ingredient of a cosmetic product (face cream). Our experimental protocol included product testing in 25 healthy females, while an emotion questionnaire, analysis of saliva samples regarding the concentration of the hormones cortisol and α-amylase and mobile EEG measurement for quantification of the alpha brain waves before and after stress induction were conducted. It was shown that with this experimental design, the sample with the ingredient produced significant stress relief, as evidenced by significantly less negative emotion, significantly lowered cortisol levels and showed a trend towards a significant increase in alpha activity compared to placebo application. Our data provide evidence that this method is suitable for analyzing the differences between the two samples. In the future, this method can be utilized in the current or a further optimized form to evaluate the psychophysiological effects of cosmetic products on humans. Full article
(This article belongs to the Section Cosmetic Dermatology)
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11 pages, 741 KiB  
Article
The Role of Preservatives and Multifunctionals on the Oxidation of Cosmetic O/W Emulsions
by Arielle Springer and Helena Ziegler
Cosmetics 2022, 9(3), 59; https://doi.org/10.3390/cosmetics9030059 - 7 Jun 2022
Cited by 4 | Viewed by 8408
Abstract
Preservatives are typically used to protect cosmetic products from microbial spoilage. However, there is evidence that some preservatives can increase oxidation in O/W emulsions. This could have disadvantages for product quality, efficacy, and consumer health and well-being. Therefore, the impact of preservatives or [...] Read more.
Preservatives are typically used to protect cosmetic products from microbial spoilage. However, there is evidence that some preservatives can increase oxidation in O/W emulsions. This could have disadvantages for product quality, efficacy, and consumer health and well-being. Therefore, the impact of preservatives or multifunctionals on oxidation should be quantified. For this purpose, five O/W emulsions with different preservatives were prepared and stored. During storage, the oxygen concentration in the headspace of the samples was studied. The samples showed significant differences in their oxygen uptake and daily oxygen consumption rate. Thus, the preservatives used in this study had an influence on oxidation. Full article
(This article belongs to the Section Cosmetic Formulations)
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