Exploring the Role of Apigenin in Neuroinflammation: Insights and Implications.

Neuroinflammation, a hallmark of various central nervous system disorders, is often associated with oxidative stress and neuronal or oligodendrocyte cell death. It is therefore very interesting to target neuroinflammation pharmacologically. One therapeutic option is the use of nutraceuticals, particularly apigenin. Apigenin is present in plants: vegetables (parsley, celery, onions), fruits (oranges), herbs (chamomile, thyme, oregano, basil), and some beverages (tea, beer, and wine). This review explores the potential of apigenin as an anti-inflammatory agent across diverse neurological conditions (multiple sclerosis, Parkinson's disease, Alzheimer's disease), cancer, cardiovascular diseases, cognitive and memory disorders, and toxicity related to trace metals and other chemicals. Drawing upon major studies, we summarize apigenin's multifaceted effects and underlying mechanisms in neuroinflammation. Our review underscores apigenin's therapeutic promise and calls for further investigation into its clinical applications.

Clinical evidence requirements according to the IVDR 2017/746: practical tools and references for underpinning clinical evidence of IVD-MDs.

In May 2022, the European Regulation 2017/746 (IVDR) came into force. It changes the approach of in vitro medical devices (IVD-MDs) for industry and institutions. It reinforces the clinical evidence requirements to improve performance, safety and transparency. Despite extended transition periods and existing guides, IVDR remains difficult to interpret and bringing devices into compliance requires efforts. The generation of clinical evidence is essential to demonstrate compliance with IVDR, and encompasses scientific validity, analytical performance and clinical performance. It is required to demonstrate, per intended use in the target population and clinical care pathway, IVD-MDs clinical performance (compared to a predefined clinical performance). Thus, there is a need for IVD-manufacturers and end-users in health care institutions, to obtain guidance on how to generate this clinical evidence. This article aims industrials and clinicians to identify key steps imposed by the IVDR for bringing IVD-MDs to the EU-market. We propose a general view of performance evaluation requirements for IVD-MDs and provide key references, including how to establish study design that will enable to document clinical performance of existing, refined or emerging medical tests. Finally, we propose a roadmap to address the relevant questions and studies in relation to the documents requested in the IVDR.

Involvement of Microglia in Neurodegenerative Diseases: Beneficial Effects of Docosahexahenoic Acid (DHA) Supplied by Food or Combined with Nanoparticles.

Neurodegenerative diseases represent a major public health issue and require better therapeutic management. The treatments developed mainly target neuronal activity. However, an inflammatory component must be considered, and microglia may constitute an important therapeutic target. Given the difficulty in developing molecules that can cross the blood-brain barrier, the use of food-derived molecules may be an interesting therapeutic avenue. Docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid (22:6 omega-3), has an inhibitory action on cell death and oxidative stress induced in the microglia. It also acts on the inflammatory activity of microglia. These data obtained in vitro or on animal models are corroborated by clinical trials showing a protective effect of DHA. Whereas DHA crosses the blood-brain barrier, nutritional intake lacks specificity at both the tissue and cellular level. Nanomedicine offers new tools which favor the delivery of DHA at the cerebral level, especially in microglial cells. Because of the biological activities of DHA and the associated nanotargeting techniques, DHA represents a therapeutic molecule of interest for the treatment of neurodegenerative diseases.

Oxysterols and multiple sclerosis: Physiopathology, evolutive biomarkers and therapeutic strategy.

Multiple sclerosis is an autoimmune disease that affects the central nervous system. Dysfunction of the immune system leads to lesions that cause motor, sensory, cognitive, visual and/or sphincter disturbances. In the long term, these disorders can progress towards an irreversible handicap. The diagnosis takes time because there are no specific criteria to diagnose multiple sclerosis. To realize the diagnosis, a combination of clinical, biological, and radiological arguments is therefore required. Hence, there is a need to identify multiple sclerosis biomarkers. Some biomarkers target immunity through the detection of oligoclonal bands, the measurement of the IgG index and cytokines. During the physiopathological process, the blood-brain barrier can be broken, and this event can be identified by measuring metalloproteinase activity and diffusion of gadolinium in the brain by magnetic resonance imaging. Markers of demyelination and of astrocyte and microglial activity may also be of interest as well as markers of neuronal damage and mitochondrial status. The measurement of different lipids in the plasma and cerebrospinal fluid can also provide suitable information. These different lipids include fatty acids, fatty acid peroxidation products, phospholipids as well as oxidized derivatives of cholesterol (oxysterols). Oxysterols could constitute new biomarkers providing information on the form of multiple sclerosis, the outcome of the disease and the answer to treatment.

In vitro interactions between bone marrow stromal cells and hippocampal slice cultures.

Bone marrow stromal cells (BMSCs) are capable of differentiating into various cell types including brain cells. Several groups have also demonstrated trophic effects of MSC grafts in experimental ischemia models. However, the underlying molecular mechanisms of these effects are not fully understood. We developed an "in vitro graft model" which consisted in a coculture of GFP-expressing BMSCs and hippocampal organotypic slice cultures. Total marrow cells (MCs) or BMSCs after one (BMSC(1P)) or five passages (BMSC(5P)) were transplanted on hippocampal slices. During the 10 days of our experiments, MCs and BMSC(1P) migrated toward the tissue, but their total number remained constant. Conversely, the number of BMSC(5P) decreased over the 10 days of the experiment, and no migration could be detected. Using immunohistochemistry, we observed that the hippocampal slices induced the expression of neural antigens in very few grafted cells, but MCs and BMSC(1P) improved the conservation of the hippocampal slice culture. Similar experiments using BMSC(5P) did not produce any significant change. We conclude that the number of passages greatly influence BMSCs survival rate, migration and neuroprotective capacities.