In Vitro Evaluation of the Effects of 7-Ketocholesterol and 7β-Hydroxycholesterol on the Peroxisomal Status: Prevention of Peroxisomal Damages and Concept of Pexotherapy.

7-Ketocholesterol and 7β-hydroxycholesterol are most often derived from the autoxidation of cholesterol. Their quantities are often increased in the body fluids and/or diseased organs of patients with age-related diseases such as cardiovascular diseases, Alzheimer's disease, age-related macular degeneration, and sarcopenia which are frequently associated with a rupture of RedOx homeostasis leading to a high oxidative stress contributing to cell and tissue damages. On murine cells from the central nervous system (158N oligodendrocytes, microglial BV-2 cells, and neuronal N2a cells) as well as on C2C12 murine myoblasts, these two oxysterols can induce a mode of cell death which is associated with qualitative, quantitative, and functional modifications of the peroxisome.

Therapeutic Applications of Oxysterols and Derivatives in Age-Related Diseases, Infectious and Inflammatory Diseases, and Cancers.

Oxysterols, resulting from the oxidation of cholesterol, are formed either by autoxidation, enzymatically, or by both processes. These molecules, which are provided in more or less important quantities depending on the type of diet, are also formed in the body and their presence is associated with a normal physiological activity. Their increase and decrease at the cellular level and in biological fluids can have significant consequences on health due or not to the interaction of some of these molecules with different types of receptors but also because oxysterols are involved in the regulation of RedOx balance, cytokinic and non-cytokinic inflammation, lipid metabolism, and induction of cell death.

Chemical and Biochemical Features of Spinasterol and Schottenol.

Phytosterols, which are produced in plants, are structurally similar to cholesterol. Their basic structures consist of a cyclo pentano-perhydrophenanthrene nucleus composed of 3 hexane rings and of a pentane ring with an alkyl side chain. There are around more than 250 phytosterols and related compounds that have been identified in natural resources.

Chemical synthesis and biochemical properties of cholestane-5α,6β-diol-3-sulfonate: A non-hydrolysable analogue of cholestane-5α,6β-diol-3β-sulfate.

Cholestane-3β,5α,6β-triol (CT) is a primary metabolite of 5,6-epoxycholesterols (5,6-EC) that is catalyzed by the cholesterol-5,6-epoxide hydrolase (ChEH). CT is a well-known biomarker for Niemann-Pick disease type C (NP-C), a progressive inherited neurodegenerative disease. On the other hand, CT is known to be metabolized by the 11β-hydroxysteroid-dehydrogenase of type 2 (11β-HSD2) into a tumor promoter named oncosterone that stimulates the growth of breast cancer tumors.

Two Argan Oil Phytosterols, Schottenol and Spinasterol, Attenuate Oxidative Stress and Restore LPS-Dysregulated Peroxisomal Functions in and Wild-Type BV-2 Microglial Cells.

Oxidative stress and inflammation are the key players in neuroinflammation, in which microglia dysfunction plays a central role. Previous studies suggest that argan oil attenuates oxidative stress, inflammation, and peroxisome dysfunction in mouse brains. In this study, we explored the effects of two major argan oil (AO) phytosterols, Schottenol (Schot) and Spinasterol (Spina), on oxidative stress, inflammation, and peroxisomal dysfunction in two murine microglial BV-2 cell lines, () and ()-deficient cells challenged with LPS treatment.

Sustainable Extraction, Chemical Profile, Cytotoxic and Antileishmanial Activities In-Vitro of Some Species Leaves Essential Oils.

Anti-leishmanial drugs extracted from natural sources have not been sufficiently explored in the literature. Until now, leishmaniasis treatments have been limited to synthetic and expensive drugs. This study investigated, for the first time, the anti-leishmanial efficacy of essential oils (EOs) from the leaves of species (, , and ).

Cytoprotective activities of representative nutrients from the Mediterranean diet and of Mediterranean oils against 7-ketocholesterol- and 7β-hydroxycholesterol-induced cytotoxicity: Application to age-related diseases and civilization diseases.

7-ketocholesterol and 7β-hydroxycholesterol are two oxysterols mainly formed by the autoxidation of cholesterol. These two molecules are interconvertible via specific enzymes. These two oxysterols are often observed at increased amounts in biological fluids as well as tissues and organs affected during age-related diseases and in diseases of civilization such as cardiovascular, neurodegenerative, and ocular diseases as well as type 2 diabetes and metabolic syndrome.

Protective effects of milk thistle (Sylibum marianum) seed oil and α-tocopherol against 7β-hydroxycholesterol-induced peroxisomal alterations in murine C2C12 myoblasts: Nutritional insights associated with the concept of pexotherapy.

Peroxisomes play an important role in regulating cell metabolism and RedOx homeostasis. Peroxisomal dysfunctions favor oxidative stress and cell death. The ability of 7β-hydroxycholesterol (7β-OHC; 50 μM, 24 h), known to be increased in patients with age-related diseases such as sarcopenia, to trigger oxidative stress, mitochondrial and peroxisomal dysfunction was studied in murine C2C12 myoblasts.

Antioxidant Properties and Cytoprotective Effect of L. Seed Oil against 7β-Hydroxycholesterol-Induced Toxicity in C2C12 Myoblasts: Reduction in Oxidative Stress, Mitochondrial and Peroxisomal Dysfunctions and Attenuation of Cell Death.

Aging is characterized by a progressive increase in oxidative stress, which favors lipid peroxidation and the formation of cholesterol oxide derivatives, including 7β-hydroxycholesterol (7β-OHC). This oxysterol, which is known to trigger oxidative stress, inflammation, and cell death, could contribute to the aging process and age-related diseases, such as sarcopenia. Identifying molecules or mixtures of molecules preventing the toxicity of 7β-OHC is therefore an important issue.

Prevention by Dietary Polyphenols (Resveratrol, Quercetin, Apigenin) Against 7-Ketocholesterol-Induced Oxiapoptophagy in Neuronal N2a Cells: Potential Interest for the Treatment of Neurodegenerative and Age-Related Diseases.

The Mediterranean diet is associated with health benefits due to bioactive compounds such as polyphenols. The biological activities of three polyphenols (quercetin (QCT), resveratrol (RSV), apigenin (API)) were evaluated in mouse neuronal N2a cells in the presence of 7-ketocholesterol (7KC), a major cholesterol oxidation product increased in patients with age-related diseases, including neurodegenerative disorders. In N2a cells, 7KC (50 µM; 48 h) induces cytotoxic effects characterized by an induction of cell death.

Prevention of 7-Ketocholesterol-Induced Overproduction of Reactive Oxygen Species, Mitochondrial Dysfunction and Cell Death with Major Nutrients (Polyphenols, ω3 and ω9 Unsaturated Fatty Acids) of the Mediterranean Diet on N2a Neuronal Cells.

The brain, which is a cholesterol-rich organ, can be subject to oxidative stress in a variety of pathophysiological conditions, age-related diseases and some rare pathologies. This can lead to the formation of 7-ketocholesterol (7KC), a toxic derivative of cholesterol mainly produced by auto-oxidation. So, preventing the neuronal toxicity of 7KC is an important issue to avoid brain damage.

Emerging practices in onboarding programs for PAs and NPs.

Objective: To describe administrative factors that should be considered when designing an onboarding program for physician assistants (PAs) and NPs.

Methods: Interview study of 13 administrators of onboarding programs. Interviews were transcribed and analyzed for themes by a team of researchers, with feedback from interviewees.

Assessment of the role of Trichomonas tenax in the etiopathogenesis of human periodontitis: A systematic review.

Objective: This systematic review was to assess the presence of Trichomonas tenax in patients with periodontitis and to elucidate its potential role in the onset and development of this disease.

Method: Systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and by consulting the five databases: Medline, Science Direct, Web of Science, Dentistry and Oral Science Sources and Cochrane Central Register of Controlled Trials. Following Koch's postulates revisited by Socransky as PICO framework, this collection data was only including full text of clinical trials concerning patients with periodontitis, case-reports and in vitro research published between 1960 and March 2019.

Empathy and Burnout - A Cross-Sectional Study Among Mental Healthcare Providers in France.

Previous studies have established a correlation between empathy and burnout among healthcare providers. The aim of this study is to explore whether empathy - the ability to understand what another person is experiencing, was related to mental healthcare staffs' burnout. We performed a descriptive, cross-sectional, observational study among medical and nursing mental healthcare staff working in the district of Moselle, France.

Biotin attenuation of oxidative stress, mitochondrial dysfunction, lipid metabolism alteration and 7β-hydroxycholesterol-induced cell death in 158N murine oligodendrocytes.

Mitochondrial dysfunction and oxidative stress are involved in neurodegenerative diseases associated with an enhancement of lipid peroxidation products such as 7β-hydroxycholesterol (7β-OHC). It is, therefore, important to study the ability of 7β-OHC to trigger mitochondrial defects, oxidative stress, metabolic dysfunctions and cell death, which are hallmarks of neurodegeneration, and to identify cytoprotective molecules. The effects of biotin were evaluated on 158N murine oligodendrocytes, which are myelin synthesizing cells, exposed to 7β-OHC (50 µM) with or without biotin (10 and 100 nM) or α-tocopherol (positive control of cytoprotection).

Advanced Materials for Next-Generation Spacecraft.

Spacecraft are expected to traverse enormous distances over long periods of time without an opportunity for maintenance, re-fueling, or repair, and, for interplanetary probes, no on-board crew to actively control the spacecraft configuration or flight path. Nevertheless, space technology has reached the stage when mining of space resources, space travel, and even colonization of other celestial bodies such as Mars and the Moon are being seriously considered. These ambitious aims call for spacecraft capable of self-controlled, self-adapting, and self-healing behavior.

Advancing In-Hospital Clinical Deterioration Prediction Models.

Background: Early warning systems lack robust evidence that they improve patients' outcomes, possibly because of their limitation of predicting binary rather than time-to-event outcomes.

Objectives: To compare the prediction accuracy of 2 statistical modeling strategies (logistic regression and Cox proportional hazards regression) and 2 machine learning strategies (random forest and random survival forest) for in-hospital cardiopulmonary arrest.

Methods: Retrospective cohort study with prediction model development from deidentified electronic health records at an urban academic medical center.

Perceptions of Workload Burden and Adherence to ABCDE Bundle Among Intensive Care Providers.

Background: Use of the interprofessional Awakening and Breathing Coordination, Delirium Monitoring and Management, and Early Mobility (ABCDE) bundle is recommended practice in intensive care, but its adoption remains limited.

Objective: To examine the relationship between intensive care unit provider attitudes regarding the ABCDE bundle and ABCDE bundle adherence.

Methods: A 1-time survey of 268 care providers in 10 intensive care units across the country who had worked at least 4 shifts per month to examine their attitudes toward workload burden, difficulty carrying out the bundle, perceived safety, confidence, and perceived strength of evidence.

A numerical study of fixed frequency reflectometry measurements of plasma filaments with radial and poloidal velocity components.

A 2D finite-differences time-domain full-wave code is used to simulate the measurements of plasma filaments with fixed frequency O-mode reflectometry. The plasma is modeled by a linear slab plasma plus a Gaussian perturbation propagating in a direction that can vary from poloidal to radial. The plasma background density gradient is chosen in agreement with the steep edge transport barrier of H-modes in the ASDEX Upgrade (AUG) tokamak.