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Objectives: This study was performed to identify predictive markers of worse outcomes in patients with severe COVID-19 in an intensive care unit. Methods: Sixty patients with severe COVID-19, hospitalized in the Intensive Care Unit (ICU) between March and July 2021, were stratified into two groups according to the outcome survivors and non-survivors. After admission to the ICU, blood samples were collected directly for biomarker analysis. Routine hematological and biochemical biomarkers, as well as serum levels of cytokines, chemokines, and immunoglobulins, were investigated. Results: Lymphopenia, neutrophilia, and thrombocytopenia were more pronounced in non-surviving patients, while the levels of CRP, AST, creatinine, ferritin, AST, troponin I, urea, magnesium, and potassium were higher in the non-surviving group than the survival group. In addition, serum levels of IL-10, CCL2, CXCL9, and CXCL10 were significantly increased in patients who did not survive. These changes in the biomarkers evaluated were associated with increased mortality in patients with severe COVID-19. Conclusion: The present study confirmed and expanded the validity of laboratory biomarkers as indicators of mortality in severe COVID-19. [ABSTRACT FROM AUTHOR]

Inflammatory responses are terminated by the clearance of dead cells, a process termed efferocytosis. A consequence of efferocytosis is the synthesis of the antiinflammatory mediators TGF-β, PGE2, and IL-10; however, the efferocytosis of infected cells favors Th17 responses by eliciting the synthesis of TGF-β, IL-6, and IL-23. Recently, we showed that the efferocytosis of apoptotic Escherichia coli-infected macrophages by dendritic cells triggers PGE2 production in addition to pro-Th17 cytokine expression. We therefore examined the role of PGE2 during Th17 differentiation and intestinal pathology. The efferocytosis of apoptotic E. coli-infected cells by dendritic cells promoted high levels of PGE2, which impaired IL-1R expression via the EP4-PKA pathway in T cells and consequently inhibited Th17 differentiation. The outcome of murine intestinal Citrobacter rodentium infection was dependent on the EP4 receptor. Infected mice treated with EP4 antagonist showed enhanced intestinal defense against C. rodentium compared with infected mice treated with vehicle control. Those results suggest that EP4 signaling during infectious colitis could be targeted as a way to enhance Th17 immunity and host defense. [ABSTRACT FROM AUTHOR]

Objectives: This study was performed to identify predictive markers of worse outcomes in patients with severe COVID-19 in an intensive care unit., Methods: Sixty patients with severe COVID-19, hospitalized in the Intensive Care Unit (ICU) between March and July 2021, were stratified into two groups according to the outcome survivors and non-survivors. After admission to the ICU, blood samples were collected directly for biomarker analysis. Routine hematological and biochemical biomarkers, as well as serum levels of cytokines, chemokines, and immunoglobulins, were investigated., Results: Lymphopenia, neutrophilia, and thrombocytopenia were more pronounced in non-surviving patients, while the levels of CRP, AST, creatinine, ferritin, AST, troponin I, urea, magnesium, and potassium were higher in the non-surviving group than the survival group. In addition, serum levels of IL-10, CCL2, CXCL9, and CXCL10 were significantly increased in patients who did not survive. These changes in the biomarkers evaluated were associated with increased mortality in patients with severe COVID-19., Conclusion: The present study confirmed and expanded the validity of laboratory biomarkers as indicators of mortality in severe COVID-19., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 dos Santos Medeiros, Sousa Lino, Perez, Sousa, Campana, Miyajima, Carvalho-Silva, Dejani, de Sousa Fernandes, Yagin, Al-Hashem, Elkholi, Alyami and Souto.)

Background and Objective: Imprinted genes are important for the offspring development. To assess the relationship between obesity-related H19DMR methylation and H19 and IGF2 gene expression and offspring growth and body composition., Methods: Thirty-nine overweight/obese and 25 normal weight pregnant women were selected from the "Araraquara Cohort Study" according to their pre-pregnancy BMI. Fetal growth and body composition and newborn growth were assessed, respectively, by ultrasound and anthropometry. The methylation of H19DMR in maternal blood, cord blood, maternal decidua and placental villi tissues was evaluated by methylation-sensitive restriction endonuclease qPCR, and H19 and IGF2 expression by relative real-time PCR quantification. Multiple linear regression models explored the associations of DNA methylation and gene expression with maternal, fetal, and newborn parameters., Results: H19DMR was less methylated in maternal blood of the overweight/obese group. There were associations of H19DMR methylation in cord blood with centiles of fetal biparietal diameter (BPD) and abdominal subcutaneous fat thickness and newborn head circumference (HC); H19DMR methylation in maternal decidua with fetal occipitofrontal diameter (OFD), HC, and length; H19DMR methylation in placental villi with fetal OFD, HC and abdominal subcutaneous fat thickness and with newborn HC. H19 expression in maternal decidua was associated with fetal BPD and femur length centiles and in placental villi with fetal OFD and subcutaneous arm fat. IGF2 expression in maternal decidua was associated with fetal BPD and in placental villi with fetal OFD., Conclusion: To our knowledge, this is the first study to demonstrate associations of imprinted genes variations at the maternal-fetal interface of the placenta and in cord blood with fetal body composition, supporting the involvement of epigenetic mechanisms in offspring growth and body composition., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Argentato, Marchesi, Dejani, Nakandakare, Teles, Batista, Leitão, Luzia, Ramos and Rondó.)

Apoptotic cell clearance by professional and nonprofessional phagocytes in the process of efferocytosis is critical to preserve tissue homeostasis. Uptake of apoptotic cells by dendritic cells generates regulatory T cells and induces immunologic tolerance against self-antigens. In contrast, ingestion of infected apoptotic cells promotes activation of TLR4/MyD88-dependent bone marrow-derived dendritic cells (BMDCs) and triggers Th17 cell differentiation. In this study, we evaluated the impact of Streptococcus pneumoniae -infected apoptotic cell efferocytosis by BMDCs derived from C57BL/6 mice on differentiation and expansion of CD4 + T cell subsets, as well as the role of TLR2/4 and receptor-interacting protein 2 (RIP2) receptors in recognizing intracellular pathogens during efferocytosis. We demonstrated that BMDC-mediated efferocytosis of S. pneumoniae -infected apoptotic cells induced Th1 cell differentiation and expansion. Although TLR2/4 and RIP2 deficiency in BMDCs did not affect Th1 cell differentiation during efferocytosis, the absence of RIP2 decreased IFN-γ production by CD4 T cells during the expansion phase. These findings suggest that RIP2-mediated IL-1β production during efferocytosis of S. pneumoniae -infected apoptotic cells partially supports a Th1-mediated IFN-γ production microenvironment., (Copyright © 2022 The Authors.)

Bioactive compounds found in food and medicinal plants contribute to maintaining health and treating illnesses. For example, hydroxycinnamic acids, such as ferulic acid, are widely present in nature and have several pharmacological properties, including antioxidant, anti-inflammatory, and beneficial effects in parameters of diabetes and hyperlipidemia. The results of studies in animal models and in vitro experiments of ferulic acid suggest its high therapeutic and preventive potential against several pathological disorders, such as cardiovascular diseases. Therefore, in this review, the bioactivities of ferulic acid on the cardiovascular system are described, including the discussion of the mechanisms of action in the various components of the system. In this review, we discuss the pharmacological properties of this versatile natural product in aspects of cardiovascular health, including cardioprotective and antihypertensive actions, and on the metabolism of lipids, diabetes, and thrombosis., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)