Extracellular vesicles act as shuttle vectors or signal transducers that can deliver specific biological information and have progressively emerged as key regulators of organized communities of cells within multicellular organisms in health and disease. Here, we survey the evolutionary origin, general characteristics, and biological significance of extracellular vesicles as mediators of intercellular signaling, discuss the various subtypes of extracellular vesicles thus far described and the principal methodological approaches to their study, and review the role of extracellular vesicles in tumorigenesis, immunity, non-synaptic neural communication, vascular-neural communication through the blood-brain barrier, renal pathophysiology, and embryo-fetal/maternal communication through the placenta.

https://www.mdpi.com/1422-0067/21/7/2514/pdf

Extracellular Vesicles as Signaling Mediators and Disease Biomarkers across Biological Barriers.

Aging - Oxidative stress, antioxidants and computational modeling.

Accumulating evidence indicates that intracellular reactive oxygen species (ROS) production is highly involved in bone homeostasis by intervening osteoclast or osteoblast differentiation. Interestingly, ROS that are known as oxidizing agents exert dose-dependent biphasic properties in bone remodeling, including preventing osteoblast activity but accelerating osteoclast resorption. ROS mainly composed of superoxide anion radical, hydroxyl radical, nitric oxide, and two-electron reduction product hydrogen peroxide, which are important components to regulate bone cell metabolism and function in mammal skeleton. These free radicals can be partly produced in bone and boosted in an inflammation state. Although numerous researches have emphasized the impacts of ROS on bone cell biology and verified the mechanism of ROS signaling cascades, the recapitulatory commentary is necessary. In this review article, we particularly focus on the regulation of the intracellular ROS and its potential mechanism impacting on cell-signaling transduction in osteoclast and osteoblast differentiation for preferable understanding the pathogenesis and searching for novel therapeutic protocols for human bone diseases.

/pdf/ros-signaling-cascades-dual-regulations-for-osteoclast-and-iifciox3wo.pdf

ROS signaling cascades: dual regulations for osteoclast and osteoblast.

Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease or Charcot disease, is a fatal neurodegenerative disease that affects motor neurons (MNs) and leads to death within 2-5 years of diagnosis, without any effective therapy available. Although the pathological mechanisms leading to ALS are still unknown, a wealth of evidence indicates that an excessive reactive oxygen species (ROS) production associated with an inefficient antioxidant defense represents an important pathological feature in ALS. Substantial evidence indicates that oxidative stress (OS) is implicated in the loss of MNs and in mitochondrial dysfunction, contributing decisively to neurodegeneration in ALS. Although the modulation of OS represents a promising approach to protect MNs from degeneration, the fact that several antioxidants with beneficial effects in animal models failed to show any therapeutic benefit in patients raises several questions that should be analyzed. Using specific queries for literature search on PubMed, we review here the role of OS-related mechanisms in ALS, including the involvement of altered mitochondrial function with repercussions in neurodegeneration. We also describe antioxidant compounds that have been mostly tested in preclinical and clinical trials of ALS, also describing their respective mechanisms of action. While the description of OS mechanism in the different mutations identified in ALS has as principal objective to clarify the contribution of OS in ALS, the description of positive and negative outcomes for each antioxidant is aimed at paving the way for novel opportunities for intervention. In conclusion, although antioxidant strategies represent a very promising approach to slow the progression of the disease, it is of utmost need to invest on the characterization of OS profiles representative of each subtype of patient, in order to develop personalized therapies, allowing to understand the characteristics of antioxidants that have beneficial effects on different subtypes of patients.

/pdf/oxidative-stress-in-amyotrophic-lateral-sclerosis-2rwe46dn8l.pdf

Oxidative Stress in Amyotrophic Lateral Sclerosis: Pathophysiology and Opportunities for Pharmacological Intervention

Abstract Extracellular vesicles (EVs) represent a diverse class of lipid bilayer membrane vesicles released by both animal and plant cells. These ubiquitous vesicles are involved in intercellular communication and transport of various biological cargos, including proteins, lipids, and nucleic acids. In recent years, interest in plant‐derived EVs has increased tremendously, as they serve as a scalable and sustainable alternative to EVs derived from mammalian sources. In vitro and in vivo findings have demonstrated that these plant‐derived vesicles (PDVs) possess intrinsic therapeutic activities that can potentially treat diseases and improve human health. In addition, PDVs can also act as efficient and biocompatible drug carriers. While preclinical studies have shown promising results, there are still several challenges and knowledge gaps that have to be addressed for the successful translation of PDVs into clinical applications, especially in view of the lack of standardised protocols for material handling and PDV isolation from various plant sources. This review provides the readers with a quick overview of the current understanding and research on PDVs, critically analysing the current challenges and highlighting the immense potential of PDVs as a novel class of therapeutics to treat human diseases. It is expected that this work will guide scientists to address the knowledge gaps currently associated with PDVs and promote new advances in plant‐based therapeutic solutions.

Plant‐derived extracellular vesicles: Recent advancements and current challenges on their use for biomedical applications

This review analyzes the relationship between microvesicles and reactive oxygen species (ROS). This relationship is bidirectional; on the one hand, the number and content of microvesicles produced by the cells are affected by oxidative stress conditions; on the other hand, microvesicles can directly and/or indirectly modify the ROS content in the extra- as well as the intracellular compartments. In this regard, microvesicles contain a pro-oxidant or antioxidant machinery that may produce or scavenge ROS: direct effect. This mechanism is especially suitable for eliminating ROS in the extracellular compartment. Endothelial microvesicles, in particular, contain a specific and well-developed antioxidant machinery. On the other hand, the molecules included in microvesicles can modify (activate or inhibit) ROS metabolism in their target cells: indirect effect. This can be achieved by the incorporation into the cells of ROS metabolic enzymes included in the microvesicles, or by the regulation of signaling pathways involved in ROS metabolism. Proteins, as well as miRNAs, are involved in this last effect.

https://tandfonline.com/doi/pdf/10.1080/20013078.2019.1626654

Microvesicles: ROS scavengers and ROS producers.

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Microvesicles: ROS scavengers and ROS producers.