Next-Generation Proteomics of Brain Extracellular Vesicles in Schizophrenia Provide New Clues on the Altered Molecular Connectome.

Extracellular vesicles (EVs) are tiny membranous structures that mediate intercellular communication. The role(s) of these vesicles have been widely investigated in the context of neurological diseases; however, their potential implications in the neuropathology subjacent to human psychiatric disorders remain mostly unknown. Here, by using next-generation discovery-driven proteomics, we investigate the potential role(s) of brain EVs (bEVs) in schizophrenia (SZ) by analyzing these vesicles from the three post-mortem anatomical brain regions: the prefrontal cortex (PFC), hippocampus (HC), and caudate (CAU). The results obtained indicate that bEVs from SZ-affected brains contain region-specific proteins that are associated with abnormal GABAergic and glutamatergic transmission. Similarly, these vesicles from the analyzed regions were implicated in synaptic decay, abnormal brain immunity, neuron structural imbalances, and impaired cell homeostasis. Our findings also provide evidence, for the first time, that networks of molecular exchange (involving the PFC, HC, and CAU) are potentially active and mediated by EVs in non-diseased brains. Additionally, these bEV-mediated networks seem to have become partially reversed and largely disrupted in the brains of subjects affected by SZ. Taken as a whole, these results open the door to the uncovering of new biological markers and therapeutic targets, based on the compositions of bEVs, for the benefit of patients affected by SZ and related psychotic disorders.

Differential systemic decellularization in vivo to study molecular changes in each vasculature layer in murine models of disease.

Vascular dysfunction underlies the onset and progression of many life-threatening diseases, highlighting the need for improved understanding of its molecular basis. Here, we present differential systemic decellularization in vivo (DISDIVO), a protocol that enables systemic and independent study of the molecular changes in each vasculature layer in murine models of disease. We describe steps for anesthesia, perfusion surgery, and exsanguination. We then detail detachment and collection of glycocalyx and decellularization and collection of both endothelial and smooth muscle cells. For complete details on the use and execution of this protocol, please refer to Serra et al., Gallart-Palau et al., and Vinaiphat et al.1,2,3.

Preclinical evaluation of PHH-1V vaccine candidate against SARS-CoV-2 in non-human primates.

SARS-CoV-2 emerged in December 2019 and quickly spread worldwide, continuously striking with an unpredictable evolution. Despite the success in vaccine production and mass vaccination programs, the situation is not still completely controlled, and therefore accessible second-generation vaccines are required to mitigate the pandemic. We previously developed an adjuvanted vaccine candidate coded PHH-1V, based on a heterodimer fusion protein comprising the RBD domain of two SARS-CoV-2 variants. Here, we report data on the efficacy, safety, and immunogenicity of PHH-1V in cynomolgus macaques. PHH-1V prime-boost vaccination induces high levels of RBD-specific IgG binding and neutralizing antibodies against several SARS-CoV-2 variants, as well as a balanced Th1/Th2 cellular immune response. Remarkably, PHH-1V vaccination prevents SARS-CoV-2 replication in the lower respiratory tract and significantly reduces viral load in the upper respiratory tract after an experimental infection. These results highlight the potential use of the PHH-1V vaccine in humans, currently undergoing Phase III clinical trials.

Altered ureido protein modification profiles in seminal plasma extracellular vesicles of non-normozoospermic men.

Introduction: Extracellular vesicles (EVs) have been recognized as key players in numerous physiological functions. These vesicles alter their compositions attuned to the health and disease states of the organism. In men, significant changes in the proteomic composition(s) of seminal plasma EVs (sEVs) have already been found to be related to infertility. Methods: Methods: In this study, we analyze the posttranslational configuration of sEV proteomes from normozoospermic (NZ) men and non-normozoospermic (non-NZ) men diagnosed with teratozoospermia and/or asthenozoospermia by unbiased, discovery-driven proteomics and advanced bioinformatics, specifically focusing on citrulline (Cit) and homocitrulline (hCit) posttranscriptional residues, both considered product of ureido protein modifications. Results and discussion: Significant increase in the proteome-wide cumulative presence of hCit together with downregulation of Cit in specific proteins related to decisive molecular functions have been encountered in sEVs of non-NZ subjects. These findings identify novel culprits with a higher chance of affecting fundamental aspects of sperm functional quality and define potential specific diagnostic and prognostic non-invasive markers for male infertility.

Plant-derived nootropics and human cognition: A systematic review.

Substances with modulatory capabilities on certain aspects of human cognition have been revered as nootropics from the dawn of time. The plant kingdom provides most of the currently available nootropics of natural origin. Here, in this systematic review, we aim to provide state-of-the-art information regarding proven and unproven effects of plant-derived nootropics (PDNs) on human cognition in conditions of health and disease. Six independent searches, one for each neurocognitive domain (NCD), were performed in parallel using three independent scientific library databases: PubMed, Cochrane and Scopus. Only scientific studies and systematic reviews with humans published between January 2000 and November 2021 were reviewed, and 256 papers were included. Ginkgo biloba was the most relevant nootropic regarding perceptual and motor functions. Bacopa monnieri improves language, learning and memory. Withania somnifera (Ashwagandha) modulates anxiety and social-related cognitions. Caffeine enhances attention and executive functions. Together, the results from the compiled studies highlight the nootropic effects and the inconsistencies regarding PDNs that require further research.Supplemental data for this article is available online at https://doi.org/10.1080/10408398.2021.2021137.

Oral Microbiota, Its Equilibrium and Implications in the Pathophysiology of Human Diseases: A Systematic Review.

Imbalances of the oral microbiota and dysbiosis have traditionally been linked to the occurrence of teeth and oral diseases. However, recent findings indicate that this microbiota exerts relevant influence in systemic health. Dysbiosis of the oral microbiota is implicated in the apparition and progression of cardiovascular, neurodegenerative and other major human diseases. In fact, the oral microbiota are the second most diverse and largely populated microbiota of the human body and its relationships with systemic health, although widely explored, they still lack of proper integration. The purpose of this systematic review is thus to widely examine the implications of oral microbiota in oral, cardiovascular and neurodegenerative diseases to offer integrative and up-to-date interpretations. To achieve that aim, we identified a total of 121 studies curated in PUBMED from the time interval January 2003-April 2022, which after careful screening resulted in 79 studies included. The reviewed scientific literature provides plausible vias of implication of dysbiotic oral microbiota in systemic human diseases, and encourages further research to continue elucidating the highly relevant and still poorly understood implications of this niche microbiota in systemic health. PROSPERO Registration Number: CRD42022299692. This systematic review follows relevant PRISMA guidelines.