COVID-19 has been considered a vascular disease, and inflammation, intravascular coagulation, and consequent thrombosis may be associated with endothelial dysfunction. These changes, in addition to hypoxia, may be responsible for pathological angiogenesis. This research investigated the impact of COVID-19 on vascular function by analyzing post-mortem lung samples from 24 COVID-19 patients, 10 H1N1pdm09 patients, and 11 controls. We evaluated, through the immunohistochemistry technique, the tissue immunoexpressions of biomarkers involved in endothelial dysfunction, microthrombosis, and angiogenesis (ICAM-1, ANGPT-2, and IL-6, IL-1β, vWF, PAI-1, CTNNB-1, GJA-1, VEGF, VEGFR-1, NF-kB, TNF-α and HIF-1α), along with the histopathological presence of microthrombosis, endothelial activation, and vascular layer hypertrophy. Clinical data from patients were also observed. The results showed that COVID-19 was associated with increased immunoexpression of biomarkers involved in endothelial dysfunction, microthrombosis, and angiogenesis compared to the H1N1 and CONTROL groups. Microthrombosis and vascular layer hypertrophy were found to be more prevalent in COVID-19 patients. This study concluded that immunothrombosis and angiogenesis might play a key role in COVID-19 progression and outcome, particularly in patients who die from the disease.
Objective: Given the high proliferative activity of germinal matrix and its direct correlation with hypoxemia, it is necessary to investigate the possible molecular regulation pathways, to understand the existing clinical relationship between the hypoxic-ischemic insult and the biomarkers NF-kB, AKT-3, Parkin, TRK-C and VEGFR-1. Methods: A hundred and eighteen germinal matrix samples of the central nervous system of patients who died in the first 28 days of life were submitted to histological and immunohistochemistry analysis to identify the tissue immunoexpression of those biomarkers related to asphyxia, prematurity, and death events within 24h. Results: A significantly increased tissue immunoexpression of NF-kB, AKT-3 and Parkin was observed in the germinal matrix of preterm infants. In addition, significantly decreased tissue immunoexpression of VEGFR-1 and NF-kB was observed in patients who experienced asphyxia followed by death within 24 hours. Conclusions: The results suggest a direct involvement between the hypoxic-ischemic insult and NF-kB and VEGFR-1 markers since a decreased immunoexpression of these biomarkers was observed in asphyxiated patients. Furthermore, it is suggested that there was not enough time for VEGFR-1 to be transcribed, translated and expressed on the surface of the plasma membrane. This temporality can be observed in the relationship between NF-kB expression and the survival time of individuals who died within 24 hours, suggesting that this factor is essential for the production of VEGFR-1 and, therefore, to carry out the necessary remodeling effect to neovascularize the affected region.
Objective: Major Depressive Disorder (MDD) has as diagnostics characteristics chronic deep sadness, anhedonia, sleeping disorder, lower energy, and cognition impairment like memory deficits. Among the pharmacological treatments that have been used until the moment, most of them act by monoaminergic pathways. Overall, the antidepressant effects promoted by this kind of medication usually delay starting, resulting in treatment resistance by the patients; moreover, in some cases, this kind of treatment has shown to be inefficient in depression remission. With this, new treatments have been studied for resistant cases and an immediate antidepressant effect, for example, ketamine – whose action occurs in glutamatergic pathways. This study aimed to analyze, from a literature review, the molecular mechanisms involved in the action of ketamine - focusing on the neuroplastic hypothesis of depression. Methods: A literature search was conducted in PubMed, MEDLINE, and SciELO databases using the following terms as descriptors: "ketamine AND depression AND neuroplasticity," with criterion PICO, resulting in 60 bibliographic texts. Results/discussion: The studies analyzed demonstrated that ketamine could exert its antidepressant effects through the inhibition of GABAergic interneurons, activation of TRK-B/AKT/mTORC pathways involved with cell survival/growth through the neurotrophine BDNF and increased activation of AMPAr by glutamate. Furthermore, it is evident that the pharmacodynamics of ketamine involves different molecular cascades present in the impaired neural plasticity pathways in individuals with MDD. Conclusion: Thus, more research on the effectiveness of ketamine is needed to consolidate its use in MDD and to evolve with glutamatergic pharmacological therapy for other mental disorders, such as bipolar and neurodegenerative affective disorders, an example of Alzheimer's disease.
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