1,275 research outputs found

    Anandamide inhibits Cdk2 and activates Chk1 leading to cell cycle arrest in human breast cancer cells.

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    AbstractThis study was designed to determine the molecular mechanisms underlying the anti-proliferative effect of the endocannabinoid anandamide on highly invasive human breast cancer cells, MDA-MB-231. We show that a metabolically stable analogue of anandamide, Met-F-AEA, induces an S phase growth arrest correlated with Chk1 activation, Cdc25A degradation and suppression of Cdk2 activity. These findings demonstrate that Met-F-AEA induced cell cycle blockade relies on modulated expression and activity of key S phase regulatory proteins. The observed mechanism of action, already reported for well-known chemotherapeutic drugs, provides strong evidence for a direct role of anandamide related compounds in the activation of cell cycle checkpoints

    The complex interplay among hepatocytes and immune cells at the crossroad between inflammation and cholesterol metabolism in hyperglycemia

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    An intriguing piece of evidence for the inflammatory story of type 2 diabetes has come to the light. A recent study by Okin and colleagues adds new clues to the interplay between cholesterol metabolism and immunity and how it impacts glucose homeostasis in inflammatory conditions. But some questions are a still unsolved conundrum. Here we suggest to better dissect the regulatory mechanism of Mevalonate pathway and to underpin a new causative link between immunometabolic dysregulation and diabetes

    The basis of the modern medical hygiene in the medieval Medical School of Salerno

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    The link between hygiene and the concept of transmission of infective diseases was established earlier than the birth of microbiology, thanks to the studies of two neglected physicians of maternity clinic, Ignác Fülöp Semmelweis and Oliver Holmes, in the mid-1800s. Surprisingly, centuries earlier, a medieval women physician, Trotula de Ruggiero, introduced for the first time the notion of diseases’ prevention, highlighting the importance of the association of personal hygiene, balanced nutrition and physical activity for better health. Moreover, she was particularly concerned of hands hygiene for the midwives during child birth, to preserve the good health of both the mother and the baby. She practiced inside the medieval Medical School of Salerno, whose main text, the “Regimen Sanitatis Salerni” has an entire part dedicated to hygiene, providing hygienic precepts that anticipate the concepts derived from the revolutionary discoveries in medical science only centuries later

    Gene Expression Analysis of Mevalonate Kinase Deficiency Affected Children Identifies Molecular Signatures Related to Hematopoiesis

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    Mevalonate kinase deficiency (MKD) is a rare autoinflammatory genetic disorder characterized by recurrent fever attacks and systemic inflammation with potentially severe complications. Although it is recognized that the lack of protein prenylation consequent to mevalonate pathway blockade drives IL1β hypersecretion, and hence autoinflammation, MKD pathogenesis and the molecular mechanisms underlaying most of its clinical manifestations are still largely unknown. In this study, we performed a comprehensive bioinformatic analysis of a microarray dataset of MKD patients, using gene ontology and Ingenuity Pathway Analysis (IPA) tools, in order to identify the most significant differentially expressed genes and infer their predicted relationships into biological processes, pathways, and networks. We found that hematopoiesis linked biological functions and pathways are predominant in the gene ontology of differentially expressed genes in MKD, in line with the observed clinical feature of anemia. We also provided novel information about the molecular mechanisms at the basis of the hematological abnormalities observed, that are linked to the chronic inflammation and to defective prenylation. Considering the broad and unspecific spectrum of MKD clinical manifestations and the difficulty in its diagnosis, a better understanding of MKD molecular bases could be translated to the clinical level to facilitate diagnosis, and improve management and therapy
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