Adina-Nicoleta Lazar

Air pollution causes around 4.2 million premature deaths worldwide every year [1]. Several studies have demonstrated the harmful effects of poor air quality on health: onset of respiratory diseases [2], cardiovascular problems [3] and neurological disorders [4]. For traffic-related pollution, exhaust emissions are widely studied and their level is actually in decrease, thanks to relevant policies. Still, this is not the case for non-exhaust emissions (brakes, tires, pavement, vehicle components and re-suspension phenomena), which account for the majority of particulate emissions [5]. In order to characterize the non-exhaust emissions and to evaluate their potential toxicity, two industrial partnerships have been set up. Indeed, braking tests were carried out in the laboratory as part of the INSA - VOLVO Chair collaborative project and additional tests were performed with a system directly integrated into the vehicle to analyze particles from tire-road contact within the framework of the INSA - MICHELIN Chair.For each test, we used an innovative collection system developed in the laboratory, allowing us to capture particles from the brakes or tires directly into a culture medium or a biomimetic surfactant (a new device developed under the Pulsalys DPPA project). This setup also includes a particle counter, with particle size range from 10 nm up to 10 µm, enabling particle size distribution analysis during the tests, along with a carbon tab for particle collection, which is subsequently examined using SEM-EDX to determine the particles’ composition. In order to identify the health impacts of the collected non-exhaust particles, the effect of the collection media on cellular viability was evaluated using RAW264 macrophages cell line. Changes in the physicochemical properties of pulmonary surfactant, as well as the biophysical properties of cells, upon contact with non-exhaust particles were also evaluated.The collected non-exhaust particles did not show a significant impact on cell viability. However, using a fluidity marker (DIOLL), we detected changes in cell biophysical properties and surfactant structure: indeed, cells in the presence of particles became more rigid, while pulmonary surfactant in the presence of particles became more fluid.This study underlines thus a significant disturbance in cell metabolism and cellular homeostasis, despite an apparently unaffected cell viability. The observed biophysical changes seem to represent an early marker of chronic pathologies such as cancer or pulmonary fibrosis. [1] Fuller et al, “Pollution and health: a progress update,” Lancet Planet Health, vol. 6, pp. 535–547, 2022.[2] Caillaud et al, “Outdoor pollution and its effects on lung health in France,’’ Revue des Maladies Respiratoires, vol. 36, p. 1150—1183, 2019.[3] Lelieveld et al, “Cardio- vascular disease burden from ambient air pollution in europe reassessed using novel hazard ratio functions.,” European Heart Journa, vol. 40, p. 1590–1596, 2019.[4] Piguet, “Neurosciences grand public pollution environnementale maladies du cerveau : Les pistes actuelles,” NeuroCampus, vol. Brochure 1, 2018.[5] Martini, “Scientific evidence on vehicle’s emissions,” The European Commission’s science and knowledge service, 2018.

We report on the U‐shaped folding of flexible guest molecules of medicinal interest upon their inclusion into macrocyclic cavity of p ‐sulfonato‐calix[4]arene in aqueous media. Alexidine and pentamidine are FDA‐approved drug compounds currently rediscovered as potent membrane‐targeting antibiotic adjuvants helping restore antibiotic activity against multidrug resistant bacteria pathogens. We have adopted host‐guest and crystal engineering approach to study these drugs with a view of potential supramolecular formulations and/or crystal forms. We focus on the host‐guest conformational and structural behaviour of alexidine and pentamidine under macrocyclic confinement conditions benefitting from single crystal X‐ray diffraction analysis, self‐assembly studies in solution by NMR spectroscopy, dynamic light scattering and atomic force microscopy, and ion mobility mass spectrometry (IM–MS) analysis complemented by theoretical calculations. Our findings show that the simple bowl‐shaped host promotes conformational fixing and crystallization of these guest molecules of high conformational freedom that are otherwise challenging to crystallize. The IM–MS structural studies of p ‐sulfonato‐calix[4]arene complexes with pentamidine and alexidine revealed significant guest reorganization in the solution/gas phase, compared to the binding modes observed in the crystal structures. Despite these changes, the host‐guest complexation remained consistent, with new interactions highlighting the increased role of electrostatic forces in the gas phase.

Stroke is a devastating neurological disorder that is characterized by the sudden disruption of blood flow to the brain. Lipids are essential components of brain structure and function and play pivotal roles in stroke pathophysiology. Dysregulation of lipid signaling pathways modulates key cellular processes such as apoptosis, inflammation, and oxidative stress, exacerbating ischemic brain injury. In the present review, we summarize the roles of lipids in stroke pathology in different models (cell cultures, animal, and human studies). Additionally, the potential of lipids, especially polyunsaturated fatty acids, to promote neuroprotection and their use as biomarkers in stroke are discussed.

The association of the APOE4 (vs. APOE3) isoform with an increased risk of Alzheimer’s disease (AD) is unequivocal, but the underlying mechanisms remain incompletely elucidated. A prevailing hypothesis incriminates the impaired ability of APOE4 to clear neurotoxic amyloid-β peptides (Aβ) from the brain as the main mechanism linking the apolipoprotein isoform to disease etiology. The APOE protein mediates lipid transport both within the brain and from the brain to the periphery, suggesting that lipids may be potential co-factors in APOE4-associated physiopathology. The present study reveals several changes in the pathways of lipid homeostasis in the brains of mice expressing the human APOE4 vs. APOE3 isoform. Carriers of APOE4 had altered cholesterol turnover, an imbalance in the ratio of specific classes of phospholipids, lower levels of phosphatidylethanolamines bearing polyunsaturated fatty acids and an overall elevation in levels of monounsaturated fatty acids. These modifications in lipid homeostasis were related to increased production of Aβ peptides as well as augmented levels of tau and phosphorylated tau in primary neuronal cultures. This suite of APOE4-associated anomalies in lipid homeostasis and neurotoxic protein levels may be related to the accrued risk for AD in APOE4 carriers and provides novel insights into potential strategies for therapeutic intervention.

The association of the APOE4 (vs APOE3) isoform with an increased risk of Alzheimer’s Disease (AD) is unequivocal, but the underlying mechanisms remain incompletely elu-cidated. A prevailing hypothesis incriminates the impaired ability of APOE4 to clear neurotoxic amyloid-β peptides (Aβ) from the brain as the main mechanism linking apolipoprotein isoform to disease aetiology. APOE protein mediates lipid transport both within the brain and from the brain to the periphery, suggesting that lipids may be potential co-factors in APOE4-associated physiopathology. The present study reveals several alterations in pathways of lipid homeostasis in the brains of mice expressing the human APOE4 versus APOE3 isoform. Carriers of APOE4 had deficient cholesterol turnover, an imbalance in the ratio of specific classes of phospholipids, lower levels of phosphatidylethanolamines bearing poly-unsaturated fatty acids and an overall eleva-tion in levels of monounsaturated fatty acids. These modifications in lipid homeostasis were related with increased production of Aβ peptides as well as augmented levels of tau and phosphorylated tau in primary neuronal cultures. This suite of AP-OE4-associated anomalies in lipid homeostasis and neurotoxic protein levels may be related to the accrued risk for AD in APOE4 carriers and provides novel insights into potential strategies for therapeutic intervention.

Emerging African countries are characterized by explosive population growth and urbanization, which threaten environmental sustainability. This study comparatively characterized ambient aerosols and assessed cytotoxicity to facilitate improving health and environmental policy. Twenty-four air samples were collected at high and low-density traffic sites in Kano State using polysulfone and stainless steel filters attached to an automated pump. The physico-chemical properties of particulate matter were determined using scanning electron microscopy and energy dispersive X-ray analysis (SEM-EDX). In vitro, their potential toxicity was assessed using macrophages and cell fixation with staining. Results showed 51.7% of particles as PM_2.5, with the highest particle concentration in mixed sites (urban and industrial). Particle classification into four groups by elemental composition and structure showed: sand particles (Si, Al, Fe, Ca, Mg, K, Na, Mo, Sr, Zr) 30–51%; other fibers 0–3%; other particles (Si, Fe, S, Mo, Zn, and other metals) 22–40%; and silicone-based fibres 23–34%. The abundant elements are: Si, Al, Ca, Ce, Ti, Fe, Cl, Pb, and Mn. The lowest viability on cytotoxicity assessment was recorded in mixed site M2. The majority of households were located within 50 m of air sampling sites. Proximity to traffic sites worsens health, as evidenced in cytotoxicity findings. We recommend improved urban planning and intensification of emissions control.

Emerging African countries are characterized by explosive population growth and urbanization, which threaten environmental sustainability. This study comparatively characterized ambient aerosols and assessed cytotoxicity to facilitate improving health and environmental policy. Twenty-four air samples were collected at high and low-density traffic sites in Kano State using polysulfone and stainless steel filters attached to an automated pump. The physico-chemical properties of particulate matter were determined using scanning electron microscopy and energy dispersive X-ray analysis (SEM-EDX). In vitro, their potential toxicity was assessed using macrophages and cell fixation with staining. Results showed 51.7% of particles as PM_2.5, with the highest particle concentration in mixed sites (urban and industrial). Particle classification into four groups by elemental composition and structure showed: sand particles (Si, Al, Fe, Ca, Mg, K, Na, Mo, Sr, Zr) 30–51%; other fibers 0–3%; other particles (Si, Fe, S, Mo, Zn, and other metals) 22–40%; and silicone-based fibres 23–34%. The abundant elements are: Si, Al, Ca, Ce, Ti, Fe, Cl, Pb, and Mn. The lowest viability on cytotoxicity assessment was recorded in mixed site M2. The majority of households were located within 50 m of air sampling sites. Proximity to traffic sites worsens health, as evidenced in cytotoxicity findings. We recommend improved urban planning and intensification of emissions control.