Uncovering the Molecular Pathways Implicated in the Anti-Cancer Activity of the Imidazoquinoxaline Derivative EAPB02303 Using a Model.

Imiqualines are analogues of the immunomodulatory drug imiquimod. EAPB02303, the lead of the second-generation imiqualines, is characterized by significant anti-tumor effects with IC50s in the nanomolar range. We used transgenic and mutant strains of two key signaling pathways (PI3K-Akt and Ras-MAPK) disrupted in human cancers to investigate the mode of action of EAPB02303.

Influence of Oleacein, an Olive Oil and Olive Mill Wastewater Phenolic Compound, on Longevity and Stress Resistance.

Oleacein, a bioactive compound of olive oil and olive mill wastewater, has one of the strongest antioxidant activities among olive phenolics. However, few reports explore the in vivo antioxidant activity of oleacein, with no clear identification of the biological pathway involved. Earlier studies have demonstrated a link between stress resistance, such as oxidative stress, and longevity.

Two distinct mechanisms lead to either oocyte or spermatocyte decrease in C. elegans after whole developmental exposure to γ-rays.

Wildlife is subject to various sources of pollution, including ionizing radiation. Adverse effects can impact the survival, growth, or reproduction of organisms, later affecting population dynamics. In invertebrates, reproduction, which directly impacts population dynamics, has been found to be the most radiosensitive endpoint.

Water in cosmetics and Caenorhabditis elegans as an alternative model for lifespan assessment.

Objective: Water, often considered a fundamental component of life, is the most commonly used ingredient in the formulation of dermocosmetic products, with waterless products being the exception. Dermocosmetic products can contain anywhere from 50% to 85% water, which contributes to their texture and specific characteristics. The chemical composition of water varies depending on its origin and can be categorized as highly mineralized or low mineralized.

Nutritional Status of Patients with Facioscapulohumeral Muscular Dystrophy.

In patients with facioscapulohumeral muscular dystrophy (FSHD), a rare genetic neuromuscular disease, reduced physical performance is associated with lower blood levels of vitamin C, zinc, selenium, and increased oxidative stress markers. Supplementation of vitamin C, vitamin E, zinc, and selenium improves the quadriceps' physical performance. Here, we compared the nutritional status of 74 women and 85 men with FSHD.

Deciphering Differential Life Stage Radioinduced Reproductive Decline in through Lipid Analysis.

Wildlife is chronically exposed to various sources of ionizing radiations, both environmental or anthropic, due to nuclear energy use, which can induce several defects in organisms. In invertebrates, reproduction, which directly impacts population dynamics, has been found to be the most radiosensitive endpoint. Understanding the underlying molecular pathways inducing this reproduction decrease can help in predicting the effects at larger scales (i.

A systems biology analysis of reproductive toxicity effects induced by multigenerational exposure to ionizing radiation in C. elegans.

Understanding the effects of chronic exposure to pollutants over generations is of primary importance for the protection of humans and the environment; however, to date, knowledge on the molecular mechanisms underlying multigenerational adverse effects is scarce. We employed a systems biology approach to analyze effects of chronic exposure to gamma radiation at molecular, tissue and individual levels in the nematode Caenorhabditis elegans. Our data show a decrease of 23% in the number of offspring on the first generation F0 and more than 40% in subsequent generations F1, F2 and F3.

Ultrastructural analysis of the dehydrated tardigrade Hypsibius exemplaris unveils an anhydrobiotic-specific architecture.

Tardigrades can cope with adverse environmental conditions by turning into anhydrobiotes with a characteristic tun shape. Tun formation is an essential morphological adaptation for tardigrade entry into the anhydrobiotic state. The tun cell structure and ultrastructure have rarely been explored in tardigrades in general and never in Hypsibius exemplaris.

Differential modification of the C. elegans proteome in response to acute and chronic gamma radiation: Link with reproduction decline.

Emission of ionizing radiation (IR) in the environment is a natural phenomenon which can be enhanced by human activities. Ecosystems are then chronically exposed to IR. But environmental risk assessment of chronic exposure suffers from a lack of knowledge.

Interplay between ionizing radiation effects and aging in C. elegans.

Living species are chronically exposed to environmental ionizing radiations from sources that can be overexpressed by nuclear accidents. In invertebrates, reproduction is the most radiosensitive studied endpoint, likely to be connected with aging. Surprisingly, aging is a sparsely investigated endpoint after chronic ionizing radiation, whereas understanding it is of fundamental interest in biology and medicine.

Defining the viability of tardigrades with a molecular sensor related to death.

The design of experimental protocols that use animal models to assess the impact of a stress on a population or to determine the life span expectancy impact can be time-consuming due to the need for direct observations of dead and living animals. These experiments are usually based on the detectable activity of animals such as food intake or mobility and can sometimes produce either under- or overestimated results. The tardigrade Hypsibius exemplaris is an emerging model for the evolutionary biology of the tardigrade phylum because of its convenient laboratory breeding and the recent introduction of new molecular tools.

Precoce and opposite response of proteasome activity after acute or chronic exposure of C. elegans to γ-radiation.

Species are chronically exposed to ionizing radiation, a natural phenomenon which can be enhanced by human activities. The induced toxicity mechanisms still remain unclear and seem depending on the mode of exposure, i.e.

Adaptation costs to constant and alternating polluted environments.

Some populations quickly adapt to strong and novel selection pressures caused by anthropogenic stressors. However, this short-term evolutionary response to novel and harsh environmental conditions may lead to adaptation costs, and evaluating these costs is important if we want to understand the evolution of resistance to anthropogenic stressors. In this experimental evolution study, we exposed populations to uranium (U populations), salt (NaCl populations) and alternating uranium/salt treatments (U/NaCl populations) and to a control environment (C populations), over 22 generations.

Pollution breaks down the genetic architecture of life history traits in Caenorhabditis elegans.

When pollution occurs in an environment, populations present suffer numerous negative and immediate effects on their life history traits. Their evolutionary potential to live in a highly stressful environment will depend on the selection pressure strengths and on the genetic structure, the trait heritability, and the genetic correlations between them. If expression of this structure changes in a stressful environment, it becomes necessary to quantify these changes to estimate the evolutionary potential of the population in this new environment.

Rapid evolutionary responses of life history traits to different experimentally-induced pollutions in Caenorhabditis elegans.

Background: Anthropogenic disturbances can lead to intense selection pressures on traits and very rapid evolutionary changes. Evolutionary responses to environmental changes, in turn, reflect changes in the genetic structure of the traits, accompanied by a reduction of evolutionary potential of the populations under selection. Assessing the effects of pollutants on the evolutionary responses and on the genetic structure of populations is thus important to understanding the mechanisms that entail specialization to novel environmental conditions or resistance to novel stressors.

Effects of chronic gamma irradiation: a multigenerational study using Caenorhabditis elegans.

The effects of chronic exposure to (137)Cs gamma radiation (dose rate ranging from 6.6 to 42.7 mGy h(-1)) on growth and reproductive ability were carried out over three generations of Caenorhabditis elegans (F0, F1, and F2).

Chicoric acid is an antioxidant molecule that stimulates AMP kinase pathway in L6 myotubes and extends lifespan in Caenorhabditis elegans.

Chicoric acid (CA) is a caffeoyl derivative previously described as having potential anti-diabetic properties. As similarities in cellular mechanism similarities between diabetes and aging have been shown, we explored on L6 myotubes the effect of CA on the modulation of intracellular pathways involved in diabetes and aging. We also determined its influence on lifespan of Caenorhabditis elegans worm (C.

Rapid phenotypic changes in Caenorhabditis elegans under uranium exposure.

Pollutants can induce selection pressures on populations, and the effects may be concentration-dependant. The main ways to respond to the stress are acclimation (i.e.

[The diversity of aging models].

Most of the signalling pathways involved in aging regulation have been recently found well conserved at various levels throughout the evolution. Taking this into account, a diversity of model organisms, including worms, rodents, and lemurs as well, allows to address different questions: how to understand the interactions between genetic and environmental factors while challenging theories of aging, to preserve hearing integrity, to fight against senescence of neural stem cells, or to explore brain fitness from gene expression to cognitive and social behavior? Here are the main issues that can be considered, stressing the complementarities of the models. The differentiation of aging physiological aspects from those induced by age-related pathologies will also be specified.

Klotho interferes with a novel FGF-signalling pathway and insulin/Igf-like signalling to improve longevity and stress resistance in Caenorhabditis elegans.

Klotho exerts anti-aging properties in mammals in two different ways. While membrane-bound Klotho, which is primarily expressed in the kidney, acts as an obligate co-receptor of FGF23 to regulate phosphate homeostasis, secreted Klotho, resulting from the shedding of the KL1-KL2 ectodomain into the bloodstream, inhibits Insulin/IGF1 signalling. However, the underlying molecular mechanisms are not fully understood.

14-3-3 regulates life span by both DAF-16-dependent and -independent mechanisms in Caenorhabditis elegans.

Caenorhabditis elegans life span, stress resistance and metabolism are regulated by the Insulin/IGF-1/DAF-2/DAF-16 pathway. DAF-16, a member of FOXO/Forkhead transcription factor family, can be targeted by 14-3-3 proteins to promote stress resistance. We have identified a 14-3-3 C.