Search

Aims: Throughout gestation, proteins in the diet are a source of essential amino acids that are crucial for proper healthy fetal growth and development. The present study was proposed to investigate the effect of high-protein diet consumption throughout pregnancy on redox homeostasis, neuroinflammatory status and amino acid levels, including homocysteine, in the male adolescent rats offspring's cerebral cortex. We also performed a battery of behavioral tests to evaluate maternal care, olfactory preference, exploratory capacity, habituation, memory, anxiety- and depression-like behavior motor activity in the offspring., Main Methods: After pregnancy confirmation, the pregnant rats were randomly divided into two groups, according to the diet: group 1, (control) standard diet containing 20 % protein, and group 2, the high-protein diet containing 50 % protein. Throughout the gestational period, the pregnant rats received experimental diets., Key Findings: Results showed an increase in homocysteine levels and neuroinflammatory mediators in the offspring's cerebral cortex from pregnant rats supplemented with a high-protein diet throughout pregnancy. Besides decreasing histidine levels in offspring's serum. The results also revealed an impairment in memory and motricity and an increase in anxiety-like behavior in the offspring supplemented with a high-protein diet throughout pregnancy. Our findings showed a significant effect of high-protein diet consumption throughout pregnancy on offspring's neurobiochemistry, which can negatively impact behavioral performance., Significance: Our results reinforce the importance of consuming a balanced diet during the gestational period, especially macronutrients such as proteins since the fetus is sensitive to the mother's diet during pregnancy which may impact the development of the offspring., Competing Interests: Declaration of competing interest The authors no competing interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Aims: Prostate cancer is the second most frequently malignancy in men worldwide. Most deaths are caused by metastasis, and tumor cell dissemination involves the interaction with endothelial cells. However, the endothelial cell signaling involved in such interaction is not entirely understood. The tumor microenvironment contains extracellular ATP, an endogenous agonist of the purinergic P2Y 2 receptor (P2Y 2 R). P2Y 2 R signaling changes endothelial cell phenotype, which may be relevant to cancer pathophysiology. Therefore, we hypothesized that P2Y 2 R activation could favor the metastatic prostate cancer cells adhesion to endothelial cells., Main Methods: For adhesion assays, confluent endothelial cells EA.hy926 were treated with P2Y 2 R agonists before adding and imaging stained DU-145 cells. Alternatively, fluorescent probes and antibodies were used to determine intracellular endothelial Ca 2+ , nitric oxide (NO), and flow cytometry assays., Key Findings: Endothelial P2Y 2 R activation with ATP, UTP, or the selective agonist 2-thio-UTP increased DU-145 cell adhesion to EA.hy926 cells. This effect required endothelial cell Ca 2+ mobilization and relied on the endothelial expression of VCAM-1 and ICAM-1. Conversely, inhibiting this proadhesive endothelial phenotype could impair DU-145 cell adhesion. To evaluate this, we chose atorvastatin based on its notable improvement of endothelial cell dysfunction. Atorvastatin blocked UTP-induced DU-145 cell adhesion to endothelial cell monolayer in a NO-dependent manner, unveiling a P2Y 2 R and NO signaling crosstalk., Significance: Endothelial P2Y 2 R signaling contributes to the adhesion of metastatic prostate cancer cells suggesting that the downstream signaling blockade by statins could be a putative mechanism to reduce prostate cancer metastasis., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Aims: Homocysteine has been linked to neurodegeneration and motor function impairments. In the present study, we evaluate the effect of chronic mild hyperhomocysteinemia on the motor behavior (motor coordination, functional performance, and muscular force) and biochemical parameters (oxidative stress, energy metabolism, gene expression and/or protein abundance of cytokine related to the inflammatory pathways and acetylcholinesterase) in the striatum and cerebellum of Wistar male rats., Main Methods: Rodents were submitted to one injection of homocysteine (0.03 μmol Hcy/g of body weight) between 30th and 60th postnatal days twice a day. After hyperhomocysteinemia induction, rats were submitted to horizontal ladder walking, beam balance, suspension, and vertical pole tests and/or euthanized to brain dissection for biochemical and molecular assays., Key Findings: Chronic mild hyperhomocysteinemia did not alter motor function, but induced oxidative stress and impaired mitochondrial complex IV activity in both structures. In the striatum, hyperhomocysteinemia decreased TNF-α gene expression and increased IL-1β gene expression and acetylcholinesterase activity. In the cerebellum, hyperhomocysteinemia increased gene expression of TNF-α, IL-1β, IL-10, and TGF-β, while the acetylcholinesterase activity was decreased. In both structures, hyperhomocysteinemia decreased acetylcholinesterase protein abundance without altering total p-NF-κB, NF-κB, Nrf-2, and cleaved caspase-3., Significance: Chronic mild hyperhomocysteinemia compromises several biochemical/molecular parameters, signaling pathways, oxidative stress, and chronic inflammation in the striatum and cerebellum of rats without impairing motor function. These alterations may be related to the mechanisms in which hyperhomocysteinemia has been linked to movement disorders later in life and neurodegeneration., (Copyright © 2021 Elsevier Inc. All rights reserved.)