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Authors = Alain Gasser ORCID = 0000-0002-2476-0157

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18 pages, 2362 KiB  
Article
T-Allele Carriers of Mono Carboxylate Transporter One Gene Polymorphism rs1049434 Demonstrate Altered Substrate Metabolization during Exhaustive Exercise
by Benedikt Gasser, Alain Dössegger, Marie-Noëlle Giraud and Martin Flück
Genes 2024, 15(7), 918; https://doi.org/10.3390/genes15070918 - 14 Jul 2024
Cited by 5 | Viewed by 1716
Abstract
Background: Polymorphism rs1049434 characterizes the nonsynonymous exchange of adenosine (A) by thymidine (T) in the gene for monocarboxylate transporter 1 (MCT1). We tested whether T-allele carriers of rs1049434 demonstrate increased accumulation of markers of metabolic strain. Methods: Physically active, healthy, young [...] Read more.
Background: Polymorphism rs1049434 characterizes the nonsynonymous exchange of adenosine (A) by thymidine (T) in the gene for monocarboxylate transporter 1 (MCT1). We tested whether T-allele carriers of rs1049434 demonstrate increased accumulation of markers of metabolic strain. Methods: Physically active, healthy, young male subjects (n = 22) conducted a power-matched one-legged cycling exercise to exhaustion. Metabolic substrates in capillary blood, selected metabolic compounds, and indices for the slow oxidative phenotype of vastus lateralis muscle were quantified in samples collected before and after exercise. The genotypes of the rs1049434 polymorphism were determined with polymerase chain reactions. Results: One-legged exercise affected the concentration of muscle metabolites entering the tricarboxylic acid cycle, such as acetyl-co-enzyme A (+448%) and acetyl-L-carnitine (+548%), muscle glycogen (−59%), and adenosine monophosphate (−39%), 30 min post-exercise. Exercise-related variability in the muscular concentration of glycogen, long-chain acyl co-enzyme As and a triglyceride, nicotinamide adenine dinucleotide (NADH), and adenosine monophosphate (AMP) interacted with rs1049434. T-allele carriers demonstrated a 39% lesser reduction in glycogen after exercise than non-carriers when NADH increased only in the non-carriers. Muscle lactate concentration was 150% higher, blood triacyl-glyceride concentration was 53% lower, and slow fiber percentage was 20% lower in T-allele carriers. Discussion: The observations suggest a higher anaerobic glycolytic strain during exhaustive exercise and a lowered lipid handling in T-allele non-carriers. Full article
(This article belongs to the Section Human Genomics and Genetic Diseases)
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17 pages, 2615 KiB  
Review
Antitumor Immune Response Triggered by Metal-Based Photosensitizers for Photodynamic Therapy: Where Are We?
by Alain C. Jung, Fabien Moinard-Butot, Chloé Thibaudeau, Gilles Gasser and Christian Gaiddon
Pharmaceutics 2021, 13(11), 1788; https://doi.org/10.3390/pharmaceutics13111788 - 26 Oct 2021
Cited by 20 | Viewed by 3599
Abstract
Metal complexes based on transition metals have rich photochemical and photophysical properties that are derived from a variety of excited state electronic configurations triggered by visible and near-infrared light. These properties can be exploited to produce powerful energy and electron transfer processes that [...] Read more.
Metal complexes based on transition metals have rich photochemical and photophysical properties that are derived from a variety of excited state electronic configurations triggered by visible and near-infrared light. These properties can be exploited to produce powerful energy and electron transfer processes that can lead to oxygen-(in)dependent photobiological activity. These principles are the basis of photodynamic therapy (PDT), which is a clinically approved treatment that offers a promising, effective, and noninvasive complementary treatment or even an alternative to treat several types of cancers. PDT is based on a reaction involving a photosensitizer (PS), light, and oxygen, which ultimately generates cytotoxic reactive oxygen species (ROS). However, skin photosensitivity, due to the accumulation of PSs in skin cells, has hampered, among other elements, its clinical development and application. Therefore, these is an increasing interest in the use of (metal-based) PSs that are more specific to tumor cells. This may increase efficacy and corollary decrease side-effects. To this end, metal-containing nanoparticles with photosensitizing properties have recently been developed. In addition, several studies have reported that the use of immunogenic/immunomodulatory metal-based nanoparticles increases the antitumor efficacy of immune-checkpoint inhibitor-based immunotherapy mediated by anti-PD-(L)1 or CTLA-4 antibodies. In this review, we discuss the main metal complexes used as PDT PSs. Lastly, we review the preclinical studies associated with metal-based PDT PSs and immunotherapies. This therapeutic association could stimulate PDT. Full article
(This article belongs to the Special Issue Metallodrugs for Targeted Cancer Therapy)
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19 pages, 5632 KiB  
Article
Transient Thermo-Mechanical Analysis of Steel Ladle Refractory Linings Using Mechanical Homogenization Approach
by Mahmoud Ali, Thomas Sayet, Alain Gasser and Eric Blond
Ceramics 2020, 3(2), 171-189; https://doi.org/10.3390/ceramics3020016 - 2 Apr 2020
Cited by 23 | Viewed by 9549
Abstract
Mortarless refractory masonry structures are widely used in the steel industry for the linings of many high-temperature industrial applications including steel ladles. The design and optimization of these components require accurate numerical models that consider the presence of joints, as well as joint [...] Read more.
Mortarless refractory masonry structures are widely used in the steel industry for the linings of many high-temperature industrial applications including steel ladles. The design and optimization of these components require accurate numerical models that consider the presence of joints, as well as joint closure and opening due to cyclic heating and cooling. The present work reports on the formulation, numerical implementation, validation, and application of homogenized numerical models for the simulation of refractory masonry structures with dry joints. The validated constitutive model has been used to simulate a steel ladle and analyze its transient thermomechanical behavior during a typical thermal cycle of a steel ladle. A 3D solution domain and enhanced thermal and mechanical boundary conditions have been used. Parametric studies to investigate the impact of joint thickness on the thermomechanical response of the ladle have been carried out. The results clearly demonstrate that the thermomechanical behavior of mortarless masonry is orthotropic and nonlinear due to the gradual closure and reopening of the joints with the increase and decrease in temperature. In addition, resulting thermal stresses increase with the increase in temperature and decrease with the increase in joint thickness. Full article
(This article belongs to the Special Issue Design, Properties, Damage and Lifetime of Refractory Ceramics)
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