Статті в журналах: "Additif E171"

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Verleysen, Eveline, Nadia Waegeneers, Frédéric Brassinne, Sandra De Vos, Isaac Ojea Jimenez, Stella Mathioudaki, and Jan Mast. "Physicochemical Characterization of the Pristine E171 Food Additive by Standardized and Validated Methods." Nanomaterials 10, no. 3 (March 24, 2020): 592. http://dx.doi.org/10.3390/nano10030592.

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E171 (titanium dioxide) is a food additive that has been authorized for use as a food colorant in the European Union. The application of E171 in food has become an issue of debate, since there are indications that it may alter the intestinal barrier. This work applied standardized and validated methodologies to characterize representative samples of 15 pristine E171 materials based on transmission electron microscopy (TEM) and single-particle inductively coupled plasma mass spectrometry (spICP-MS). The evaluation of selected sample preparation protocols allowed identifying and optimizing the critical factors that determine the measurement of the particle size distribution by TEM. By combining optimized sample preparation with method validation, a significant variation in the particle size and shape distributions, the crystallographic structure (rutile versus anatase), and the physicochemical form (pearlescent pigments versus anatase and rutile E171) was demonstrated among the representative samples. These results are important for risk assessment of the E171 food additive and can contribute to the implementation of the European Food Safety Authority (EFSA) guidance on risk assessment of the application of nanoscience and nanotechnologies in the food and feed chain.

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Hwang, Ji-Soo, Jin Yu, Hyoung-Mi Kim, Jae-Min Oh, and Soo-Jin Choi. "Food Additive Titanium Dioxide and Its Fate in Commercial Foods." Nanomaterials 9, no. 8 (August 16, 2019): 1175. http://dx.doi.org/10.3390/nano9081175.

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Titanium dioxide (TiO2) is one of the most extensively utilized food additives (E171) in the food industry. Along with nanotechnology development, the concern about the presence of nanostructured particles in E171 TiO2 and commercial food products is growing. In the present study, the physicochemical properties of commercially available E171 TiO2 particles, including particle size distribution, were investigated, followed by their cytotoxicity and intestinal transport evaluation. The fate determination and quantification of E171 TiO2 in commercial foods were carried out based on the analytical procedure developed using simulated foods. The results demonstrated that TiO2 is a material mainly composed of particles larger than 100 nm, but present as an agglomerated or aggregated particle in commercial foods with amounts of less than 1% (wt/wt). Titanium dioxide particles generated reactive oxygen species and inhibited long-term colony formation, but the cytotoxicity was not related to particle size distribution or particle type (food- or general-grade). All TiO2 particles were mainly transported by microfold (M) cells, but also by intestinal tight junction. These findings will be useful for TiO2 application in the food industry and predicting its potential toxicity.

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Ferrante, Margherita, Alfina Grasso, Rossella Salemi, Massimo Libra, Barbara Tomasello, Maria Fiore, and Chiara Copat. "DNA Damage and Apoptosis as In-Vitro Effect Biomarkers of Titanium Dioxide Nanoparticles (TiO2-NPs) and the Food Additive E171 Toxicity in Colon Cancer Cells: HCT-116 and Caco-2." International Journal of Environmental Research and Public Health 20, no. 3 (January 21, 2023): 2002. http://dx.doi.org/10.3390/ijerph20032002.

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This study investigated the DNA damage and apoptosis in colon cancer cells HCT-116 and Caco-2 induced by engineered titanium dioxide nanoparticles (TiO2-NPs) (60 nm) and titanium dioxide food additive E171. MTT assays showed that both chemical forms significantly reduced cancer cell viability in a dose-dependent manner. In particular the food additive E171 induced a pronounced inhibitory effect on the growth of HCT-116 and Caco-2 cell lines (E171 IC50: 3.45 mg/L for HTC-116 and 1.88 mg/L Caco-2; TiO2-NPs 60 nm IC50: 41.1 mg/L for HTC-116 and 14.3 mg/L for Caco-2). A low level of genotoxicity was observed in Caco-2 cells, especially when treated with TiO2 60 nm. Western blot analysis showed that HCT116 and Caco-2 treated cells did not overexpress apoptotic markers such as cleaved Caspase 3 and cleaved Parp. Moreover, further analysis by quantitative real-time PCR (qRT-PCR) showed that TiO2-NPs and E171 did not promote the expression of Bax or downregulation of Bcl-2, nor did they increase the Bax/Bcl-2 ratio. The assay data provide clear evidence that TiO2 can cause DNA damage but does not induce apoptosis or decrease long-term cell proliferation. In addition, the results show that E171 has a slightly higher level of cytotoxicity and genotoxicity. This suggests that exposure to E171 may be hazardous to health and that further research on biological effects is needed to promote safer practices in the use of this compound.

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Bischoff, Nicolaj S., Héloïse Proquin, Marlon J. Jetten, Yannick Schrooders, Marloes C. M. Jonkhout, Jacco J. Briedé, Simone G. van Breda, et al. "The Effects of the Food Additive Titanium Dioxide (E171) on Tumor Formation and Gene Expression in the Colon of a Transgenic Mouse Model for Colorectal Cancer." Nanomaterials 12, no. 8 (April 7, 2022): 1256. http://dx.doi.org/10.3390/nano12081256.

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Titanium dioxide (TiO2) is present in many different food products as the food additive E171, which is currently scrutinized due to its potential adverse effects, including the stimulation of tumor formation in the gastrointestinal tract. We developed a transgenic mouse model to examine the effects of E171 on colorectal cancer (CRC), using the Cre-LoxP system to create an Apc-gene-knockout model which spontaneously develops colorectal tumors. A pilot study showed that E171 exposed mice developed colorectal adenocarcinomas, which were accompanied by enhanced hyperplasia in epithelial cells, lymphatic nodules at the base of the polyps, and increased tumor size. In the main study, tumor formation was studied following the exposure to 5 mg/kgbw/day of E171 for 9 weeks (Phase I). E171 exposure showed a statistically nonsignificant increase in the number of colorectal tumors in these transgenic mice, as well as a statistically nonsignificant increase in the average number of mice with tumors. Gene expression changes in the colon were analyzed after exposure to 1, 2, and 5 mg/kgbw/day of E171 for 2, 7, 14, and 21 days (Phase II). Whole-genome mRNA analysis revealed the modulation of genes in pathways involved in the regulation of gene expression, cell cycle, post-translational modification, nuclear receptor signaling, and circadian rhythm. The processes associated with these genes might be involved in the enhanced tumor formation and suggest that E171 may contribute to tumor formation and progression by modulation of events related to inflammation, activation of immune responses, cell cycle, and cancer signaling.

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Tsareva, Anastasiya A., Olga V. Egorova, Yuliya V. Demidova, and Nataliya A. Ilyushina. "Studying the ability of the food additive E171 (titanium dioxide) to induce gene mutations in bacteria." Hygiene and sanitation 102, no. 12 (December 28, 2023): 1361–66. http://dx.doi.org/10.47470/0016-9900-2023-102-12-1361-1366.

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Introduction. Titanium dioxide in the Russian Federation is approved for use in the food industry, in the production of medicines and hygiene products. The food additive E171 is a mixture of micro- and nanoparticles of TiO2. In 2010, IARC classified TiO2 in nanoform as a probably carcinogenic to humans (Group 2B). In vitro and in vivo studies of the genotoxicity of titanium dioxide revealed contradictory results, indicating both the presence and absence of TiO2 mutagenicity. The aim of the work is to evaluate the mutagenicity of the food additive E171 in the Ames test using standard and modified protocols. Materials and methods. The ability of food additive E171 (China) to induce reverse gene mutations in 5 strains of Salmonella typhimurium was studied under standard and modified conditions (cultivation of bacteria in the presence of methylated b-cyclodextrin (MCD) and/or pre-incubation for 1 hour in potassium phosphate buffer, pH 5.5 containing 10 mM NaCl and/or 3M MCD). Results. A sample of food additive E171 based on rutile titanium dioxide does not induce gene mutations in S. typhimurium in standard experiments. Modification of the Ames test protocol (decrease of the incubation mixture pH, addition of 10 mM NaCl) revealed statistically significant dose-dependent effects in TA100, TA98, and TA97 strains under metabolic incubation conditions. However, the fold increase of the number of revertants in the experimental plates compared to the negative control was < 2. Limitations. The research is limited to the mutagenicity assessment of food additive E171 (titanium dioxide) in the Ames test. Conclusion. The evaluation of the mutagenicity of titanium dioxide in other in vitro and in vivo tests taking into account the size and shape of the particles, is necessary to resolve the issue of its genetic safety as a food dye. A full range of studies will be performed on other samples of titanium dioxide presented in the market of the Russian Federation.

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Brassinne, F., S. De Vos, E. Verleysen, P. J. De Temmerman, M. Ledecq, and J. Mast. "Characterization of the TiO2 E171 food additive." Toxicology Letters 295 (October 2018): S208. http://dx.doi.org/10.1016/j.toxlet.2018.06.909.

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7

Dorier, Marie, David Béal, Céline Tisseyre, Caroline Marie-Desvergne, Muriel Dubosson, Frédérick Barreau, Eric Houdeau, Nathalie Herlin-Boime, Thierry Rabilloud, and Marie Carriere. "The food additive E171 and titanium dioxide nanoparticles indirectly alter the homeostasis of human intestinal epithelial cells in vitro." Environmental Science: Nano 6, no. 5 (2019): 1549–61. http://dx.doi.org/10.1039/c8en01188e.

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8

Rudometkina, T. F. "PHOTOMETRIC DETERMINATION OF E171 ADDITIVE IN FOOD PRODUCTS." EurasianUnionScientists 5, no. 63 (2019): 56–59. http://dx.doi.org/10.31618/esu.2413-9335.2019.5.63.177.

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9

Song, In-Gyu, Kanghee Kim, Hakwon Yoon, and June Woo Park. "Toxicity assessment of food additive (E171) in aquatic environments." Environmental Biology Research 41, no. 1 (March 30, 2023): 41–53. http://dx.doi.org/10.11626/kjeb.2023.41.1.041.

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Pannek, Carolin, Karina R. Tarantik, Laura Engel, Thomas Vetter, and Jürgen Wöllenstein. "Gasochromic Detection of NO2 on the Example of the Food Additive E141 (ii)." Proceedings 2, no. 13 (December 4, 2018): 721. http://dx.doi.org/10.3390/proceedings2130721.

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We present our investigation on the gasochromic reaction of E141 (ii) towards the toxic gas nitrogen dioxide (NO2). E141 (ii) is a chlorophyllin-based food additive, typically used as green coloring for nearly all kinds of sweets. In this presentation we show an alternative approach for using E141 (ii) as optical gas indicator. All solid samples are prepared by multi-layer screen printing on different substrates like paper and PE-foil. Gas measurements are performed using an UV/Vis spectrometer. The influence of the substrate and according layer thickness is shown.

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Baranowska-Wójcik, Ewa, Klaudia Gustaw, Dominik Szwajgier, Patryk Oleszczuk, Bożena Pawlikowska-Pawlęga, Jarosław Pawelec, and Justyna Kapral-Piotrowska. "Four Types of TiO2 Reduced the Growth of Selected Lactic Acid Bacteria Strains." Foods 10, no. 5 (April 25, 2021): 939. http://dx.doi.org/10.3390/foods10050939.

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Food-grade titanium dioxide (TiO2) containing a nanoparticle fraction (TiO2 NPs -nanoparticles) is widely used as a food additive (E171 in the EU). In recent years, it has increasingly been raising controversies as to the presence or absence of its harmful effects on the gastrointestinal microbiota. The complexity and variability of microbiota species present in the human gastrointestinal tract impede the assessment of the impact of food additives on this ecosystem. As unicellular organisms, bacteria are a very convenient research model for investigation of the toxicity of nanoparticles. We examined the effect of TiO2 (three types of food-grade E171 and one TiO2 NPs, 21 nm) on the growth of 17 strains of lactic acid bacteria colonizing the human digestive tract. Each bacterial strain was treated with TiO2 at four concentrations (60, 150, 300, and 600 mg/L TiO2). The differences in the growth of the individual strains were caused by the type and concentration of TiO2. It was shown that the growth of a majority of the analyzed strains was decreased by the application of E171 and TiO2 NPs already at the concentration of 150 and 300 mg/L. At the highest dose (600 mg/L) of the nanoparticles, the reactions of the bacteria to the different TiO2 types used in the experiment varied.

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Grasso, Alfina, Margherita Ferrante, Pietro Zuccarello, Tommaso Filippini, Giovanni Arena, Maria Fiore, Antonio Cristaldi, Gea Oliveri Conti, and Chiara Copat. "Chemical Characterization and Quantification of Titanium Dioxide Nanoparticles (TiO2-NPs) in Seafood by Single-Particle ICP-MS: Assessment of Dietary Exposure." International Journal of Environmental Research and Public Health 17, no. 24 (December 20, 2020): 9547. http://dx.doi.org/10.3390/ijerph17249547.

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The significant increase in the production and variety of nanoparticles (NPs) has led to their release into the environment, especially into the marine environment. Titanium dioxide nanoparticles (TiO2-NPs) are used in different industrial sectors, from the food industry to several consumer and household products. Since the aquatic environment is highly sensitive to contamination by TiO2-NPs, this work aimed to give a preliminary assessment of the contamination of packaged seafood, where the food additive TiO2 (E171) is not to be intentionally added. This allowed providing a chemical characterization and quantification of TiO2-NPs in processed canned fish products belonging to different trophic positions of the pelagic compartment and in canned clam. The new emerging technique called single-particle inductively coupled plasma mass spectrometry (spICP-MS) was applied, which allows the determination of nanoparticle number-based concentration, as well as the dissolved titanium. This study highlights how processed food, where the pigment E171 was not intentionally added, contains TiO2 in its nanoparticle form, as well as dissolved titanium. Processed clam represented the seafood with the highest content of TiO2-NPs. In pelagic fish species, we found progressively higher levels and smaller sizes of TiO2-NPs from smaller to larger fish. Our results highlight the importance of planning the characterization and quantification of TiO2-NPs in food both processed and not, as well as where the pigment E171 is intentionally added and not, as it is not the only source of TiO2-NPs. This result represents a solid step toward being able to estimate the real level of dietary exposure to TiO2-NPs for the general population and the related health risks.

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Waegeneers, Nadia, Sandra De Vos, Eveline Verleysen, Ann Ruttens, and Jan Mast. "Estimation of the Uncertainties Related to the Measurement of the Size and Quantities of Individual Silver Nanoparticles in Confectionery." Materials 12, no. 17 (August 22, 2019): 2677. http://dx.doi.org/10.3390/ma12172677.

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E174 (silver) is a food additive that may contain silver nanoparticles (AgNP). Validated methods are needed to size and quantify these particles in a regulatory context. However, no validations have yet been performed with food additives or real samples containing food additives requiring a sample preparation step prior to analysis. A single-particle inductively coupled plasma mass spectrometry (spICP-MS) method was developed and validated for sizing and quantifying the fraction of AgNP in E174 and in products containing E174, and associated uncertainties related to sample preparation, analysis and data interpretation were unraveled. The expanded measurement uncertainty for AgNP sizing was calculated to be 16% in E174-containing food products and increased up to 23% in E174 itself. The E174 food additives showed a large silver background concentration combined with a relatively low number of nanoparticles, making data interpretation more challenging than in the products. The standard uncertainties related to sample preparation, analysis, and challenging data interpretation were respectively 4.7%, 6.5%, and 6.0% for triplicate performances. For a single replicate sample, the uncertainty related to sample preparation increased to 6.8%. The expanded measurement uncertainty related to the concentration determination was 25–45% in these complex samples, without a clear distinction between additives and products. Overall, the validation parameters obtained for spICP-MS seem to be fit for the purpose of characterizing AgNP in E174 or E174-containing products.

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Krivobok, V. S., A. V. Kolobov, S. E. Dimitrieva, S. I. Chentsov, S. N. Nikolaev, N. V. Ivanov, M. A. Chernopitssky, D. A. Litvinov, M. A. Shevchenko, and S. F. Umanskaya. "Raman Markers of Toxic Nanofraction in Anatase TiO2 Micropowder Used as E171 Food Additive." Journal of Russian Laser Research 42, no. 4 (July 2021): 388–98. http://dx.doi.org/10.1007/s10946-021-09974-1.

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Proquin, Héloïse, Marlon J. Jetten, Marloes C. M. Jonkhout, Luis G. Garduño-Balderas, Jacob J. Briedé, Theo M. de Kok, Yolanda I. Chirino, and Henk van Loveren. "Gene expression profiling in colon of mice exposed to food additive titanium dioxide (E171)." Food and Chemical Toxicology 111 (January 2018): 153–65. http://dx.doi.org/10.1016/j.fct.2017.11.011.

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Proquin, Héloïse, Carolina Rodríguez-Ibarra, Carolyn G. J. Moonen, Ismael M. Urrutia Ortega, Jacob J. Briedé, Theo M. de Kok, Henk van Loveren, and Yolanda I. Chirino. "Titanium dioxide food additive (E171) induces ROS formation and genotoxicity: contribution of micro and nano-sized fractions." Mutagenesis 32, no. 1 (October 27, 2016): 139–49. http://dx.doi.org/10.1093/mutage/gew051.

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Proquin, Héloïse, Carolina Rodríguez-Ibarra, Carolyn Moonen, Ismael M. Urrutia Ortega, Jacob J. Briedé, Theo M. de Kok, Henk van Loveren, and Yolanda Irasema Chirino. "Titanium dioxide food additive (E171) induces ROS formation and genotoxicity: contribution of micro and nano-sized fractions." Mutagenesis 33, no. 3 (May 2018): 267–68. http://dx.doi.org/10.1093/mutage/gey011.

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De Vos, Sandra, Nadia Waegeneers, Eveline Verleysen, Karen Smeets, and Jan Mast. "Physico-chemical characterisation of the fraction of silver (nano)particles in pristine food additive E174 and in E174-containing confectionery." Food Additives & Contaminants: Part A 37, no. 11 (September 18, 2020): 1831–46. http://dx.doi.org/10.1080/19440049.2020.1809719.

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Blaznik, Urška, Sanja Krušič, Maša Hribar, Anita Kušar, Katja Žmitek, and Igor Pravst. "Use of Food Additive Titanium Dioxide (E171) before the Introduction of Regulatory Restrictions Due to Concern for Genotoxicity." Foods 10, no. 8 (August 17, 2021): 1910. http://dx.doi.org/10.3390/foods10081910.

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Food-grade titanium dioxide (TiO2; E171) is a coloring food additive. In May 2021, a scientific opinion was published by the European Food Safety Authority concluding that TiO2 can no longer be considered as a safe food additive. Our aim was to investigate the trends in the use of TiO2 in the food supply. A case study was conducted in Slovenia using two nationally representative cross-sectional datasets of branded foods. Analysis was performed on N = 12,644 foods (6012 and 6632 in 2017 and 2020, respectively) from 15 food subcategories where TiO2 was found as a food additive. A significant decrease was observed in the use of TiO2 (3.6% vs. 1.8%; p < 0.01). TiO2 was most often used in the chewing gum category (36.3%) in 2017, and chocolate and sweets category (45.9%) in 2020. Meanwhile, in 2017, the largest share of TiO2-containing foods was observed in the chewing gum category, namely, 70.3%, and these products presented over 85% of the market share. In 2020, only 24.6% of chewing gums contained TiO2, which accounted for only 3% of the market share. In conclusion, we showed an overall decrease in TiO2 use, even though it has not yet been officially removed from the list of authorized food additives.

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Bellani, Lorenza, Simonetta Muccifora, Francesco Barbieri, Eliana Tassi, Monica Ruffini Castiglione, and Lucia Giorgetti. "Genotoxicity of the food additive E171, titanium dioxide, in the plants Lens culinaris L. and Allium cepa L." Mutation Research/Genetic Toxicology and Environmental Mutagenesis 849 (January 2020): 503142. http://dx.doi.org/10.1016/j.mrgentox.2020.503142.

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Bischoff, Nicolaj S., Theo M. de Kok, Dick T. H. M. Sijm, Simone G. van Breda, Jacco J. Briedé, Jacqueline J. M. Castenmiller, Antoon Opperhuizen, et al. "Possible Adverse Effects of Food Additive E171 (Titanium Dioxide) Related to Particle Specific Human Toxicity, Including the Immune System." International Journal of Molecular Sciences 22, no. 1 (December 28, 2020): 207. http://dx.doi.org/10.3390/ijms22010207.

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Titanium dioxide (TiO2) is used as a food additive (E171) and can be found in sauces, icings, and chewing gums, as well as in personal care products such as toothpaste and pharmaceutical tablets. Along with the ubiquitous presence of TiO2 and recent insights into its potentially hazardous properties, there are concerns about its application in commercially available products. Especially the nano-sized particle fraction (<100 nm) of TiO2 warrants a more detailed evaluation of potential adverse health effects after ingestion. A workshop organized by the Dutch Office for Risk Assessment and Research (BuRO) identified uncertainties and knowledge gaps regarding the gastrointestinal absorption of TiO2, its distribution, the potential for accumulation, and induction of adverse health effects such as inflammation, DNA damage, and tumor promotion. This review aims to identify and evaluate recent toxicological studies on food-grade TiO2 and nano-sized TiO2 in ex-vivo, in-vitro, and in-vivo experiments along the gastrointestinal route, and to postulate an Adverse Outcome Pathway (AOP) following ingestion. Additionally, this review summarizes recommendations and outcomes of the expert meeting held by the BuRO in 2018, in order to contribute to the hazard identification and risk assessment process of ingested TiO2.

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Brugiroux, Sandrine, Thomas Sauvaitre, Gwenaelle Roche, Célia Ledieu, Caroline Chevarin, Catherine Godfraind, Christophe Massard, et al. "Su1976 – Impacts of Additive Food E171 (Titanium Dioxide) on the Gut Microbiota and Colorectal Carcinogenesis in ApcMIN/+ Murine Model." Gastroenterology 156, no. 6 (May 2019): S—679. http://dx.doi.org/10.1016/s0016-5085(19)38610-x.

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Zucchetti, Andrés E., Ismael R. Barosso, Andrea Boaglio, José M. Pellegrino, Elena J. Ochoa, Marcelo G. Roma, Fernando A. Crocenzi та Enrique J. Sánchez Pozzi. "Prevention of estradiol 17β-d-glucuronide–induced canalicular transporter internalization by hormonal modulation of cAMP in rat hepatocytes". Molecular Biology of the Cell 22, № 20 (15 жовтня 2011): 3902–15. http://dx.doi.org/10.1091/mbc.e11-01-0047.

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In estradiol 17β-d-glucuronide (E17G)–induced cholestasis, the canalicular hepatocellular transporters bile salt export pump (Abcb11) and multidrug-resistance associated protein 2 (Abcc2) undergo endocytic internalization. cAMP stimulates the trafficking of transporter-containing vesicles to the apical membrane and is able to prevent internalization of these transporters in estrogen-induced cholestasis. Hepatocyte levels of cAMP are regulated by hormones such as glucagon and adrenaline (via the β2 receptor). We analyzed the effects of glucagon and salbutamol (a β2 adrenergic agonist) on function and localization of Abcb11 and Abcc2 in isolated rat hepatocyte couplets exposed to E17G and compared the mechanistic bases of their effects. Glucagon and salbutamol partially prevented the impairment in Abcb11 and Abcc2 transport capacity. E17G also induced endocytic internalization of Abcb11 and Abcc2, which partially colocalized with the endosomal marker Rab11a. This effect was completely prevented by salbutamol, whereas some transporter-containing vesicles remained internalized and mainly colocalizing with Rab11a in the perinuclear region after incubation with glucagon. Glucagon prevention was dependent on cAMP-dependent protein kinase (PKA) and independent of exchange proteins activated directly by cAMP (Epac) and microtubules. In contrast, salbutamol prevention was PKA independent and Epac/MEK and microtubule dependent. Anticholestatic effects of glucagon and salbutamol were additive in nature. Our results show that increases in cAMP could activate different anticholestatic signaling pathways, depending on the hormonal mediator involved.

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Gmoshinski, I. V., O. V. Bagryantseva, and S. A. Khotimchenko. "Toxicological and hygienic assessment of titanium dioxide nanoparticles as a component of E171 food additive (review of the literature and metahanalysis)." Health Risk Analysis, no. 2 (June 2019): 145–63. http://dx.doi.org/10.21668/health.risk/2019.2.17.

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Gmoshinski, I. V., O. V. Bagryantseva, and S. A. Khotimchenko. "Toxicological and hygienic assessment of titanium dioxide nanoparticles as a component of E171 food additive (review of the literature and metahanalysis)." Health Risk Analysis, no. 2 (June 2019): 145–63. http://dx.doi.org/10.21668/health.risk/2019.2.17.eng.

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Talamini, Laura, Sara Gimondi, Martina B. Violatto, Fabio Fiordaliso, Federica Pedica, Ngoc Lan Tran, Giovanni Sitia, et al. "Repeated administration of the food additive E171 to mice results in accumulation in intestine and liver and promotes an inflammatory status." Nanotoxicology 13, no. 8 (July 22, 2019): 1087–101. http://dx.doi.org/10.1080/17435390.2019.1640910.

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Warheit, D. "P24-38: EFSA Made a Manifest Error on the Safety of Titanium Dioxide (E171) Particles as a Food Additive for Humans." Toxicology Letters 384 (September 2023): S279. http://dx.doi.org/10.1016/s0378-4274(23)00920-7.

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Williams, Sally R., Tareq A. Juratli, Brandyn A. Castro, Tyler T. Lazaro, Corey M. Gill, Naema Nayyar, Matthew R. Strickland, et al. "Genomic Analysis of Posterior Fossa Meningioma Demonstrates Frequent AKT1 E17K Mutations in Foramen Magnum Meningiomas." Journal of Neurological Surgery Part B: Skull Base 80, no. 06 (January 10, 2019): 562–67. http://dx.doi.org/10.1055/s-0038-1676821.

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Objective Posterior fossa meningiomas are surgically challenging tumors that are associated with high morbidity and mortality. We sought to investigate the anatomical distribution of clinically actionable mutations in posterior fossa meningioma to facilitate identifying patients amenable for systemic targeted therapy trials. Methods Targeted sequencing of clinically targetable AKT1, SMO, and PIK3CA mutations was performed in 61 posterior fossa meningioma using Illumina NextSeq 500 to a target depth of >500 × . Samples were further interrogated for 53 cancer-relevant RNA fusions by the Archer FusionPlex panel to detect gene rearrangements. Results AKT1 (E17K) mutations were detected in five cases (8.2%), four in the foramen magnum and one in the cerebellopontine angle. In contrast, none of the posterior fossa tumors harbored an SMO (L412F) or a PIK3CA (E545K) mutation. Notably, the majority of foramen magnum meningiomas (4/7, 57%) harbored an AKT1 mutation. In addition, common clinically targetable gene fusions were not detected in any of the cases. Conclusion A large subset of foramen magnum meningiomas harbor AKT1 E17K mutations and are therefore potentially amenable to targeted medical therapy. Genotyping of foramen magnum meningiomas may enable more therapeutic alternatives and guide their treatment decision process.

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Fang, Luo. "The Effectiveness and Safety of 42°C Pulsed Radiofrequency Combined with 60°C Continuous Radiofrequency for Refractory Infraorbital Neuralgia: A Prospective Study." Pain Physician 3, no. 22;3 (May 11, 2019): E171—E179. http://dx.doi.org/10.36076/ppj/2019.22.e171.

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Background: Infraorbital neuralgia, one of the rare causes of facial pain, lacks systematic treatment guidelines because few studies on the topic have been published. We previously found that 42°C percutaneous nondestructive pulsed radiofrequency (PRF) treatment could achieve satisfactory pain relief for infraorbital neuralgia patients. However, patients who responded poorly to PRF had no other ideal treatment options until now. Recently, standard PRF combined with 60°C continuous radiofrequency (CRF) was successfully performed on trigeminal neuralgia patients and achieved a promising effective rate with mild complications. However, the efficacy of the combined therapy in the treatment of infraorbital neuralgia has not yet been reported. Objectives: To evaluate the effectiveness and safety of 42°C PRF combined with 60°C CRF in infraorbital neuralgia patients who responded poorly to 42°C PRF and were reluctant to receive destructive therapies or nerve decompression surgery. Study Design: Prospective, single-center, observational clinical trial. Setting: The interventional pain management center in Beijing Tiantan Hospital. Methods: We prospectively investigated the effects of 10 minutes of 3-dimensional computer tomography-guided 42°C PRF combined with 270 seconds of 60°C CRF in the treatment of 28 patients with refractory infraorbital neuralgia. The response criterion was a postoperative verbal pain numeric rating scale score reduction of > 50%. The response rates at different time points during a 2-year follow-up were calculated. Results: The effective rates of combined PRF and CRF treatment were 95.5%, 86.4%, 81.8%, 72.7%, 72.7%, and 72.7% postoperative at 1 month, 3 months, 6 months, 1 year, 18 months, and 2 years, respectively. Except for 16 patients (72.7%) experiencing mild numbness that gradually disappeared within 1 week to 2 months after the operation, no obvious complications were observed. Limitations: This study examined the therapeutic effectiveness over a period of only 2 years; no further follow-up was conducted. In addition, this study is a single-center observational clinical study with small sample sizes. Conclusions: For patients with intractable infraorbital neuralgia, 42°C PRF combined with 60°C CRF is an effective and safe treatment. Prospective, double-blind randomized controlled trials with longer follow-up periods are needed to evaluate whether the combined treatment could become an alternative option for those who do not respond to conservative treatment, sparing those patients from destructive therapies or more invasive nerve decompression surgery. Key words: Infraorbital neuralgia, effectiveness, safety, pulsed radiofrequency, continuous radiofrequency, combined therapy

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30

Dorier, Marie, Céline Tisseyre, Fanny Dussert, David Béal, Marie-Edith Arnal, Thierry Douki, Vanessa Valdiglesias, et al. "Toxicological impact of acute exposure to E171 food additive and TiO2 nanoparticles on a co-culture of Caco-2 and HT29-MTX intestinal cells." Mutation Research/Genetic Toxicology and Environmental Mutagenesis 845 (September 2019): 402980. http://dx.doi.org/10.1016/j.mrgentox.2018.11.004.

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31

Zhang, Zeli, Qinyong Gu, Ananda Ayyappan Jaguva Vasudevan, Manimehalai Jeyaraj, Stanislaw Schmidt, Jörg Zielonka, Mario Perković, et al. "Vif Proteins from Diverse Human Immunodeficiency Virus/Simian Immunodeficiency Virus Lineages Have Distinct Binding Sites in A3C." Journal of Virology 90, no. 22 (August 31, 2016): 10193–208. http://dx.doi.org/10.1128/jvi.01497-16.

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ABSTRACTLentiviruses have evolved the Vif protein to counteract APOBEC3 (A3) restriction factors by targeting them for proteasomal degradation. Previous studies have identified important residues in the interface of human immunodeficiency virus type 1 (HIV-1) Vif and human APOBEC3C (hA3C) or human APOBEC3F (hA3F). However, the interaction between primate A3C proteins and HIV-1 Vif or natural HIV-1 Vif variants is still poorly understood. Here, we report that HIV-1 Vif is inactive against A3Cs of rhesus macaques (rhA3C), sooty mangabey monkeys (smmA3C), and African green monkeys (agmA3C), while HIV-2, African green monkey simian immunodeficiency virus (SIVagm), and SIVmac Vif proteins efficiently mediate the depletion of all tested A3Cs. We identified that residues N/H130 and Q133 in rhA3C and smmA3C are determinants for this HIV-1 Vif-triggered counteraction. We also found that the HIV-1 Vif interaction sites in helix 4 of hA3C and hA3F differ. Vif alleles from diverse HIV-1 subtypes were tested for degradation activities related to hA3C. The subtype F-1 Vif was identified to be inactive for degradation of hA3C and hA3F. The residues that determined F-1 Vif inactivity in the degradation of A3C/A3F were located in the C-terminal region (K167 and D182). Structural analysis of F-1 Vif revealed that impairing the internal salt bridge of E171-K167 restored reduction capacities to A3C/A3F. Furthermore, we found that D101 could also form an internal interaction with K167. Replacing D101 with glycine and R167 with lysine in NL4-3 Vif impaired its counteractivity to A3F and A3C. This finding indicates that internal interactions outside the A3 binding region in HIV-1 Vif influence the capacity to induce degradation of A3C/A3F.IMPORTANCEThe APOBEC3 restriction factors can serve as potential barriers to lentiviral cross-species transmissions. Vif proteins from lentiviruses counteract APOBEC3 by proteasomal degradation. In this study, we found that monkey-derived A3C, rhA3C and smmA3C, were resistant to HIV-1 Vif. This was determined by A3C residues N/H130 and Q133. However, HIV-2, SIVagm, and SIVmac Vif proteins were found to be able to mediate the depletion of all tested primate A3C proteins. In addition, we identified a natural HIV-1 Vif (F-1 Vif) that was inactive in the degradation of hA3C/hA3F. Here, we provide for the first time a model that explains how an internal salt bridge of E171-K167-D101 influences Vif-mediated degradation of hA3C/hA3F. This finding provides a novel way to develop HIV-1 inhibitors by targeting the internal interactions of the Vif protein.

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32

Tassinari, Roberta, Alessia Tammaro, Andrea Martinelli, Mauro Valeri, and Francesca Maranghi. "Sex-Specific Effects of Short-Term Oral Administration of Food-Grade Titanium Dioxide Nanoparticles in the Liver and Kidneys of Adult Rats." Toxics 11, no. 9 (September 13, 2023): 776. http://dx.doi.org/10.3390/toxics11090776.

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Titanium dioxide (TiO2) nanomaterial is used in several items (implant materials, pills composition, cosmetics, etc.). Although TiO2 is no longer considered safe as a food additive, the general population is exposed daily through different routes, and information is lacking on some aspects of animal and human health. This study evaluated liver and kidney toxicity of food-grade TiO2 nanoparticles (NPs) (primary size < 25 nm) in male and female rats that were orally exposed for 5 days to 0, 1, and 2 mg/kg body weight per day (comparable with daily E171 consumption). Selected liver and kidney toxicity endpoints included serum biomarkers, histopathological analysis and expression of osteopontin (SPP1), vascular endothelial growth factor (VEGF), interleukin 6 (IL-6), and neuropeptide Y (NPY). Although TiO2 NPs are known to affect the gastric mucosa, short-term exposure induced sex-specific effects: general toxicity parameters were predominantly altered in female rats, whereas the liver appeared to be more affected than the kidneys in male rats, which also showed overexpression of NPY and SPP1. In the kidneys, the TiO2 NP effects were quantitatively similar but qualitatively different in the two sexes. In conclusion, careful consideration should be paid to the presence of TiO2 NPs in other items that can lead to human exposure.

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33

Bucher, Guillaume, Hind El Hadri, Océane Asensio, François Auger, Josefa Barrero, and Jean-Philippe Rosec. "Large-scale screening of E171 food additive (TiO2) on the French market from 2018 to 2022: Occurrence and particle size distribution in various food categories." Food Control 155 (January 2024): 110102. http://dx.doi.org/10.1016/j.foodcont.2023.110102.

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34

Baranowska-Wójcik, Ewa, Dominik Szwajgier, Izabela Jośko, Bożena Pawlikowska-Pawlęga, and Klaudia Gustaw. "Smoothies Reduce the “Bioaccessibility” of TiO2 (E 171) in the Model of the In Vitro Gastrointestinal Tract." Nutrients 14, no. 17 (August 25, 2022): 3503. http://dx.doi.org/10.3390/nu14173503.

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The food colorant E171 (TiO2) containing nano fractions can cause potential health problems. In the presented work, we used a “gastrointestinal tract” model (oral→large intestine) to “digest” a fruit smoothie in the presence of TiO2 nanoparticles and the Lactiplantibacillus plantarum B strain. The TiO2 migration was measured using the microfiltration membrane (0.2 µm; model of “TiO2 bioacessability”). We observed that the addition of the smoothie reduced the Ti content in the microfiltrate (reduced “bioacessability”) at the “mouth”, “stomach” and “large intestine” stages, probably due to the entrapment of Ti by the smoothie components. A significant decrease in Ti “bioaccessibility” at the “gastric” stage may have resulted from the agglomeration of nanoparticles at a low pH. Additionally, the presence of bacterial cells reduced the “bioaccessibility” at the “large intestine” stage. Microscopic imaging (SEM) revealed clear morphological changes to the bacterial cells in the presence of TiO2 (altered topography, shrunk-deformed cells with collapsed walls due to leakage of the content, indentations). Additionally, TiO2 significantly reduced the growth of the tested bacteria. It can be stated that the interactions (most probably entrapment) of TiO2 in the food matrix can occur during the digestion. This can influence the physicochemical properties, bioavailability and in vivo effect of TiO2. Research aimed at understanding the interactions between TiO2 and food components is in progress.

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35

Laisney, Jérôme, Mireille Chevallet, Caroline Fauquant, Camille Sageot, Yohann Moreau, Daniela Predoi, Nathalie Herlin-Boime, Colette Lebrun, and Isabelle Michaud-Soret. "Ligand-Promoted Surface Solubilization of TiO2 Nanoparticles by the Enterobactin Siderophore in Biological Medium." Biomolecules 12, no. 10 (October 19, 2022): 1516. http://dx.doi.org/10.3390/biom12101516.

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Titanium dioxide nanoparticles (TiO2-NPs) are increasingly used in consumer products for their particular properties. Even though TiO2 is considered chemically stable and insoluble, studying their behavior in biological environments is of great importance to figure their potential dissolution and transformation. The interaction between TiO2-NPs with different sizes and crystallographic forms (anatase and rutile) and the strong chelating enterobactin (ent) siderophore was investigated to look at a possible dissolution. For the first time, direct evidence of anatase TiO2-NP surface dissolution or solubilization (i.e., the removal of Ti atoms located at the surface) in a biological medium by this siderophore was shown and the progressive formation of a hexacoordinated titanium–enterobactin (Ti–ent) complex observed. This complex was characterized by UV–visible and Fourier transform infrared (FTIR) spectroscopy (both supported by Density Functional Theory calculations) as well as electrospray ionization mass spectrometry (ESI-MS) and X-ray photoelectron spectroscopy (XPS). A maximum of ca. 6.3% of Ti surface atoms were found to be solubilized after 24 h of incubation, releasing Ti–ent complexes in the micromolar range that could then be taken up by bacteria in an iron-depleted medium. From a health and environmental point of view, the effects associated to the solubilization of the E171 TiO2 food additive in the presence of enterobactin and the entrance of the Ti–enterobactin complex in bacteria were questioned.

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36

Wang, Yidan, Allan Sauvat, Celine Lacrouts, Jérôme Lebeau, Romain Grall, Marie Hullo, Fabrice Nesslany, and Sylvie Chevillard. "TiO2 Nanomaterials Non-Controlled Contamination Could Be Hazardous for Normal Cells Located in the Field of Radiotherapy." International Journal of Molecular Sciences 21, no. 3 (January 31, 2020): 940. http://dx.doi.org/10.3390/ijms21030940.

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Among nanomaterials (NMs), titanium dioxide (TiO2) is one of the most manufactured NMs and can be found in many consumers’ products such as skin care products, textiles and food (as E171 additive). Moreover, due to its most attractive property, a photoactivation upon non-ionizing UVA radiation, TiO2 NMs is widely used as a decontaminating agent. Uncontrolled contaminations by TiO2 NMs during their production (professional exposure) or by using products (consumer exposure) are rather frequent. So far, TiO2 NMs cytotoxicity is still a matter of controversy depending on biological models, types of TiO2 NMs, suspension preparation and biological endpoints. TiO2 NMs photoactivation has been widely described for UV light radiation exposure, it could lead to reactive oxygen species production, known to be both cyto- and genotoxic on human cells. After higher photon energy exposition, such as X-rays used for radiotherapy and for medical imaging, TiO2 NMs photoactivation still occurs. Importantly, the question of its hazard in the case of body contamination of persons receiving radiotherapy was never addressed, knowing that healthy tissues surrounding the tumor are indeed exposed. The present work focuses on the analysis of human normal bronchiolar cell response after co-exposition TiO2 NMs (with different coatings) and ionizing radiation. Our results show a clear synergistic effect, in terms of cell viability, cell death and oxidative stress, between TiO2 NMS and radiation.

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37

Idris, ElSorra E., Domingo J. Iglesias, Manuel Talon, and Rainer Borriss. "Tryptophan-Dependent Production of Indole-3-Acetic Acid (IAA) Affects Level of Plant Growth Promotion by Bacillus amyloliquefaciens FZB42." Molecular Plant-Microbe Interactions® 20, no. 6 (June 2007): 619–26. http://dx.doi.org/10.1094/mpmi-20-6-0619.

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Phytohormone-like acting compounds previously have been suggested to be involved in the phytostimulatory action exerted by the plant-beneficial rhizobacterium Bacillus amyloliquefaciens FZB42. Analyses by high-performance liquid chromatography and gas chromatography-mass spectrometry performed with culture filtrates of FZB42 demonstrated the presence of indole-3-acetic acid (IAA), corroborating it as one of the pivotal plant-growth-promoting substances produced by this bacterium. In the presence of 5 mM tryptophan, a fivefold increase in IAA secretion was registered. In addition, in the trp auxotrophic strains E101 (ΔtrpBA) and E102 (ΔtrpED), and in two other strains bearing knockout mutations in genes probably involved in IAA metabolism, E103 (ΔysnE, putative IAA transacetylase) and E105 (ΔyhcX, putative nitrilase), the concentration of IAA in the culture filtrates was diminished. Three of these mutant strains were less efficient in promoting plant growth, indicating that the Trp-dependent synthesis of auxins and plant growth promotion are functionally related in B. amyloliquefaciens.

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38

Espada-Bernabé, Elena, Gustavo Moreno-Martín, Beatriz Gómez-Gómez, and Yolanda Madrid. "Assesing the behaviour of particulate/nanoparticulate form of E171 (TiO2) food additive in colored chocolate candies before and after in vitro oral ingestion by spICP-MS, TEM and cellular in vitro models." Food Chemistry 432 (January 2024): 137201. http://dx.doi.org/10.1016/j.foodchem.2023.137201.

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39

Sharp, T. A., G. W. Reed, M. Sun, N. N. Abumrad, and J. O. Hill. "Relationship between aerobic fitness level and daily energy expenditure in weight-stable humans." American Journal of Physiology-Endocrinology and Metabolism 263, no. 1 (July 1, 1992): E121—E128. http://dx.doi.org/10.1152/ajpendo.1992.263.1.e121.

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The relationship between exercise and energy expenditure is unclear, with some suggestions that exercise leads to increased energy expenditure over and beyond the increase due to the exercise itself. In this cross-sectional study, we examined the relationships among aerobic fitness level, body composition, and total daily energy expenditure in 78 subjects. Daily energy expenditure (determined in a whole room calorimeter) was significantly correlated with both fat-free mass (FFM) and aerobic fitness (estimated from maximum aerobic capacity or VO2max). However, multiple-regression analysis demonstrated that, after accounting for FFM, VO2max did not explain a significant amount of the remaining variation in energy expenditure. In addition, the relationship between resting metabolic rate and both FFM and VO2max was evaluated using data from 214 weight-stable subjects analyzed retrospectively. The results were identical with the results obtained from the 78 subjects in that VO2max did not have effects independent of FFM on energy expenditure. We conclude that aerobic fitness does not have a direct effect on energy expenditure. However, it may have effects that are mediated through body composition, since in both populations studied here, VO2max was positively correlated with FFM and negatively correlated with adiposity.

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40

Watanabe, Richard M., Garry M. Steil, and Richard N. Bergman. "Critical evaluation of the combined model approach for estimation of prehepatic insulin secretion." American Journal of Physiology-Endocrinology and Metabolism 274, no. 1 (January 1, 1998): E172—E183. http://dx.doi.org/10.1152/ajpendo.1998.274.1.e172.

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The combined model approach uses kinetic analysis of both plasma insulin and C-peptide dynamics to estimate prehepatic insulin secretion rates and parameters of insulin and C-peptide kinetics. The original model used single-compartment kinetics to describe both insulin and C-peptide despite knowledge that C-peptide follows two-compartment kinetics. The performance of the model under rapidly changing secretory conditions has come into question. Thus a more complex combined model is introduced, incorporating two-compartmental C-peptide disappearance. The addition of two-compartment C-peptide kinetics required a novel numerical approach to allow estimation of model parameters. This simulation study was undertaken to 1) compare the performance of the original combined model and 2) examine the numerical method used to identify parameters for the extended combined model with two-compartment C-peptide kinetics under simulated conditions of rapidly changing insulin and C-peptide. Monte Carlo simulation revealed that the original combined model does not provide accurate estimates of prehepatic insulin secretion under rapid kinetics. However, the extended combined model provides accurate reconstruction of prehepatic insulin secretory profile without separate quantification of C-peptide kinetics.

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41

Branco, Marcelo, Miriam Ribeiro, Nubio Negrão, and Antonio C. Bianco. "3,5,3′-Triiodothyronine actively stimulates UCP in brown fat under minimal sympathetic activity." American Journal of Physiology-Endocrinology and Metabolism 276, no. 1 (January 1, 1999): E179—E187. http://dx.doi.org/10.1152/ajpendo.1999.276.1.e179.

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To investigate the role of type II 5′-deiodinase (5′D-II) in the expression of mitochondrial uncoupling protein (UCP) in brown adipose tissue (BAT), we injected intact male rats with reverse (r) 3,5,3′-triiodothyronine (T3; 100 μg ⋅ 100 g body wt−1 ⋅ day−1), an inhibitor of 5′D-II, for 2–5 days. UCP decreased by ∼20% in rats kept at 28°C and failed to increase during cold exposure (4°C). Next, thyroxine treatment (1–10 μg ⋅ 100 g body wt−1 ⋅ day−1) increased nuclear T3 in rats kept at 28 or 4°C. In these rats, nuclear T3 correlated positively with UCP. In addition, T3 (1–50 μg ⋅ 100 g body wt−1 ⋅ day−1) given to intact rats (5–15 days; 28°C) induced an approximately twofold increase in UCP. In these T3-treated animals, the interscapular BAT thermal response to norepinephrine infusion also correlated positively with T3 dose and UCP content. Treatment with propranolol or reserpine failed to block the T3 induction of UCP (∼1.8- and ∼2.3-fold). The results emphasize the importance of local 5′D-II and reveal an independent role of T3 in the expression of UCP.

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42

Zhou, Lin, Lu Wang, Jialing Zhang, Jiahe Li, Shuju Bai, Junfeng Ma, and Xueqi Fu. "Didymin improves UV irradiation resistance in C. elegans." PeerJ 6 (January 9, 2019): e6218. http://dx.doi.org/10.7717/peerj.6218.

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Didymin, a type of flavono-o-glycoside compound naturally present in citrus fruits, has been reported to be an effective anticancer agent. However, its effects on stress resistance are unclear. In this study, we treated Caenorhabditis elegans with didymin at several concentrations. We found that didymin reduced the effects of UV stressor on nematodes by decreasing reactive oxygen species levels and increasing superoxide dismutase (SOD) activity. Furthermore, we found that specific didymin-treated mutant nematodes daf-16(mu86) & daf-2(e1370), daf-16(mu86), akt-1(ok525), akt-2(ok393), and age-1(hx546) were susceptible to UV irradiation, whereas daf-2(e1371) was resistant to UV irradiation. In addition, we found that didymin not only promoted DAF-16 to transfer from cytoplasm to nucleus, but also increased both protein and mRNA expression levels of SOD-3 and HSP-16.2 after UV irradiation. Our results show that didymin affects UV irradiation resistance and it may act on daf-2 to regulate downstream genes through the insulin/IGF-1-like signaling pathway.

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43

ABDULLAHI, Xhabir, Gafur XHABIRI, Erhan SULEJMANI, and Faton SELIMI. "The effect of some additives on the rheology of dough and quality of bread." Acta agriculturae Slovenica 118, no. 2 (July 8, 2022): 1. http://dx.doi.org/10.14720/aas.2022.118.2.2601.

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The technology of production of baking products today can not be imagined without the use of food additives. In this research it was aimed to investigate the use of some additives in wheat flour type 500 for bread production. The formulations and additives used in this study are: without additives for M0, emulsifiers (E 472e) for M1, calcium phosphate (E341 ii) for M2, L-ascorbic acid (E300) for M3 and Damil additive complex (antifouling E170 - 0.06 %; emulsifier E472e -0.08 %; antioxidant E300 -0.01 %; fungal a-amylase - 0.01 %) for M4 formulation. The results showed that the use of additives positively affects some rheological qualities such as water absorption capacity, stability and energy of the dough. M4 bread had a higher specific volume than all breads with 5.14 cm 3 g-1, while M1 and M3 breads were similar. From the total points accumulated for the sensory qualities the M4 bread with a total of 88.8 points accumulated had the best qualities with volume, external appearance and very good crust and crumb taste. It is therefore recommended to use the Damil additive complex in bread production.

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Salhanick, A. I., and J. M. Amatruda. "Role of sialic acid in insulin action and the insulin resistance of diabetes mellitus." American Journal of Physiology-Endocrinology and Metabolism 255, no. 2 (August 1, 1988): E173—E179. http://dx.doi.org/10.1152/ajpendo.1988.255.2.e173.

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Adipocytes treated with neuraminidase show markedly reduced responsiveness to insulin without any alteration in insulin binding. In addition, several studies have separately demonstrated both insulin resistance and decreases in membrane sialic acid content and associated biosynthetic enzymes in diabetes mellitus. In the present study, we investigated the role that sialic acid residues may play in insulin action and in the hepatic insulin resistance associated with nonketotic diabetes. Primary cultures of hepatocytes from normal rats treated with neuraminidase demonstrated a dose-dependent decrease in insulin-stimulated lipogenesis. At a concentration of neuraminidase that decreases insulin action by 50%, 23% of total cellular sialic acid content was released. Neuraminidase-releasable sialic acid was significantly decreased in hepatocytes from diabetic rats and this was associated with significant insulin resistance. Treatment of hepatocytes from diabetic rats with cytidine 5'-monophospho-N-acetylneuraminic acid (CMP-NANA) enhanced insulin responsiveness 39%. The enhanced insulin responsiveness induced by CMP-NANA was blocked by cytidine 5'-monophosphate (CMP) suggesting that the CMP-NANA effect was catalyzed by a cell surface sialyltransferase. CMP reduced neuraminidase-releasable [14C]sialic acid incorporation into hepatocytes by 43%. The data demonstrate a role for cell surface sialic acid residues in hepatic insulin action and support a role for decreased cell surface sialic acid residues in the insulin resistance of diabetes mellitus.

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45

Murray, F. T., R. D. Johnson, M. Sciadini, M. J. Katovich, J. Rountree, and H. Jewett. "Erectile and copulatory dysfunction in chronically diabetic BB/WOR rats." American Journal of Physiology-Endocrinology and Metabolism 263, no. 1 (July 1, 1992): E151—E157. http://dx.doi.org/10.1152/ajpendo.1992.263.1.e151.

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The pituitary-testicular axis, penile reflexes, and copulatory behavior were studied in male BB diabetic rats from 10 to 40 wk of diabetes. Serum testosterone was diminished from 18 to 28 wk of diabetes, and the responses to human chorionic gonadotropin stimulation were blunted. Serum luteinizing hormone (LH) in diabetic rats did not differ from that of the control rats before or after LH-releasing hormone stimulation. Serum follicle-stimulating hormone and prolactin levels were also similar to controls. After 26 wk of diabetes, androgen-sensitive reproductive accessory organs were significantly reduced in size. This also was true for the androgen-sensitive bulbocavernosus and ischiocavernosus muscles. Penile reflexes in these animals from 20 to 32 wk of diabetes were consistently reduced in number and demonstrated prolonged latency. Copulatory behavior was evaluated in these animals at 25 and 28 wk of diabetes and revealed a reduced number of BB diabetic rats showing normal behavior at 25 wk of diabetes. At 28 wk of diabetes, mount latency, intromission latency, ejaculatory latency, and the postejaculatory interval were all prolonged compared with controls. In addition, the number of diabetic animals showing normal behavior was reduced compared with controls. These studies demonstrate that chronically BB diabetic rats develop diminished testosterone and erectile dysfunction that precedes ejaculatory dysfunction in a similar fashion as impotence in diabetic men. We suggest that further studies in this animal model may be critical to the better understanding and treatment of impotence in diabetic men.

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46

Karinch, A. M., S. R. Kimball, T. C. Vary, and L. S. Jefferson. "Regulation of eukaryotic initiation factor-2B activity in muscle of diabetic rats." American Journal of Physiology-Endocrinology and Metabolism 264, no. 1 (January 1, 1993): E101—E108. http://dx.doi.org/10.1152/ajpendo.1993.264.1.e101.

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Peptide-chain initiation is inhibited in fast-twitch skeletal muscle, but not heart, of diabetic rats. We have investigated mechanisms that might maintain eukaryotic initiation factor (eIF)-2B activity, preventing loss of efficiency of protein synthesis in heart of diabetic rats but not in fast-twitch skeletal muscle. There was no change in the amount or phosphorylation state of eIF-2 in skeletal or cardiac muscle during diabetes. In contrast, eIF-2B activity was decreased in fast-twitch but not slow-twitch muscle from diabetic animals. NADP+ inhibited partially purified eIF-2B in vitro, but addition of equimolar NADPH reversed the inhibition. The NADPH-to-NADP+ ratio was unchanged in fast-twitch muscle after induction of diabetes but was increased in heart of diabetic rats, suggesting that NADPH also prevents inhibition of eIF-2B in vivo. The activity of casein kinase II, which can phosphorylate and activate eIF-2B in vitro, was significantly lower in extracts of fast-twitch, but not cardiac muscle, of diabetic rats compared with controls. The results presented here demonstrate that changes in eIF-2 alpha phosphorylation are not responsible for the effect of diabetes on eIF-2B activity in fast-twitch skeletal muscle. Modulation of casein kinase II activity may be a factor in the regulation of protein synthesis in muscle during acute diabetes. The activity of eIF-2B in heart might be maintained by the increased NADPH/NADP+.

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47

Lewis, Gary F., Mladen Vranic, and Adria Giacca. "Role of free fatty acids and glucagon in the peripheral effect of insulin on glucose production in humans." American Journal of Physiology-Endocrinology and Metabolism 275, no. 1 (July 1, 1998): E177—E186. http://dx.doi.org/10.1152/ajpendo.1998.275.1.e177.

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We have shown previously that the greater suppression of endogenous glucose production (GP) with equimolar peripheral vs. portal insulin cannot be detected or is minimally reversed when the insulin-induced suppression of either free fatty acids (FFA) or glucagon alone is prevented. The present experiments were designed to minimize the insulin suppression of both glucagon and FFA in an attempt to further examine the mechanism of insulin’s peripheral effect on GP. In nine healthy men, we investigated the effect of limiting the insulin suppression of both FFA and glucagon by infusing heparin (250 U/h), Intralipid 10% (25 ml/h), and glucagon (0.65 ng ⋅ kg−1 ⋅ min−1) during 1) portal ( n = 9), 2) equimolar peripheral ( n = 9), and 3) half-dose peripheral insulin delivery ( n = 4) by use of our previously published tolbutamide infusion method, with calculation and matching of insulin secretion rate. GP decreased by 57.2 ± 2.6% with portal, 39.0 ± 4.1% with equimolar peripheral, and 31.5 ± 2.7% with half-dose peripheral insulin delivery ( P < 0.001 for portal vs. peripheral and P < 0.001 for portal vs. half-dose peripheral). In contrast, in six control subjects in whom glucagon and FFA were not replaced, GP decreased by 62.6 ± 2.4% with portal ( n = 6), 75.7 ± 3.0% with peripheral ( n = 6), and 56.3 ± 3.0% with half-dose peripheral ( n = 4) insulin delivery ( P < 0.01 for portal vs. peripheral and P = not significant for portal vs. half-dose peripheral). In summary, the greater suppression of GP with equimolar peripheral vs. portal insulin is eliminated and markedly reversed if the acute insulin-induced suppression of both plasma FFA and glucagon is minimized. This suggests that the insulin-induced suppression of glucagon and FFA has additive or cooperative effects in mediating the acute extrahepatic effect of insulin on GP.

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Pagliassotti, Michael J., Jione Kang, Jeffrey S. Thresher, Chin K. Sung, and Michael E. Bizeau. "Elevated basal PI 3-kinase activity and reduced insulin signaling in sucrose-induced hepatic insulin resistance." American Journal of Physiology-Endocrinology and Metabolism 282, no. 1 (January 1, 2002): E170—E176. http://dx.doi.org/10.1152/ajpendo.2002.282.1.e170.

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Sucrose feeding reduces the ability of insulin to suppress glucose production and hepatic gluconeogenesis. The present study examined the effect of a high-sucrose diet on early insulin-signaling steps in the liver. Rats were provided a high-starch (STD, control diet) or high-sucrose diet (HSD) for 3 wk. On the day of study, overnight-fasted rats were anesthetized and injected with either saline ( n = 5/diet group) or insulin (2 mU/kg, n = 5/diet group) via the portal vein. Portal venous blood and liver tissue were harvested 2 min after injections. Portal vein plasma glucose levels were not significantly different among groups, pooled average 147 ± 12 mg/dl. Western blot analysis revealed no significant differences in the amount of insulin receptor (IR), insulin receptor substrates-1 and -2 (IRS-1, IRS-2), and the p85 subunit of phosphatidylinositol (PI) 3-kinase. In contrast, the amount of the p110β subunit of PI 3-kinase was increased ∼2-fold in HSD vs. STD ( P < 0.05). After saline injection, tyrosine phosphorylation (pY) of IR, IRS-1, and IRS-2 was not significantly different between groups. However, PI 3-kinase activity associated with phosphorylated proteins was increased ∼40% in HSD vs. STD ( P < 0.05). After insulin injection, pY of the IR was not different between groups, whereas pY of IRS-1 and IRS-2 was reduced ( P < 0.05) in HSD vs. STD. In addition, association of IRS-1 and IRS-2 with p85 was significantly reduced in HSD vs. STD. These data demonstrate that an HSD impairs insulin-stimulated early postreceptor signaling (pY of IRS proteins, IRS interaction with p85). Furthermore, the increased amount of p110β and increased basal PI 3-kinase activity suggest a diet-induced compensatory response.

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49

Bischoff, Nicolaj, Héloïse Proquin, Marlon Jetten, Yannick Schrooders, Marloes Jonkhout, Jacco Briedé, Simone van Breda, et al. "Correction: Bischoff et al. The Effects of the Food Additive Titanium Dioxide (E171) on Tumor Formation and Gene Expression in the Colon of a Transgenic Mouse Model for Colorectal Cancer. Nanomaterials 2022, 12, 1256." Nanomaterials 13, no. 21 (October 31, 2023): 2888. http://dx.doi.org/10.3390/nano13212888.

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50

Rivero, Matías, Constanza Torres-Paris, Rodrigo Muñoz, Ricardo Cabrera, Claudio A. Navarro, and Carlos A. Jerez. "Inorganic Polyphosphate, Exopolyphosphatase, andPho84-Like Transporters May Be Involved in Copper Resistance inMetallosphaera sedulaDSM 5348T." Archaea 2018 (2018): 1–12. http://dx.doi.org/10.1155/2018/5251061.

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Polyphosphates (PolyP) are linear polymers of orthophosphate residues that have been proposed to participate in metal resistance in bacteria and archaea. In addition of having a CopA/CopB copper efflux system, the thermoacidophilic archaeonMetallosphaera sedulacontains electron-dense PolyP-like granules and a putative exopolyphosphatase (PPXMsed,Msed_0891) and four presumedpho84-like phosphate transporters (Msed_0846,Msed_0866,Msed_1094, andMsed_1512) encoded in its genome. In the present report, the existence of a possible PolyP-based copper-resistance mechanism inM. sedulaDSM 5348Twas evaluated.M. sedulaDSM 5348Taccumulated high levels of phosphorous in the form of granules, and its growth was affected in the presence of 16 mM copper. PolyP levels were highly reduced after the archaeon was subjected to an 8 mM CuSO4shift. PPXMsedwas purified, and the enzyme was found to hydrolyze PolyPin vitro. Essential residues for catalysis of PPXMsedwere E111 and E113 as shown by a site-directed mutagenesis of the implied residues. Furthermore,M. sedula ppx,pho84-like, andcopTMAgenes were upregulated upon copper exposure, as determined by qRT-PCR analysis. The results obtained support the existence of a PolyP-dependent copper-resistance system that may be of great importance in the adaptation of this thermoacidophilic archaeon to its harsh environment.

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