A new p65 isoform that bind the glucocorticoid hormone and is expressed in inflammation liver diseases and COVID-19

Inflammation is a physiological process whose deregulation causes some diseases including cancer. Nuclear Factor kB (NF-kB) is a family of ubiquitous and inducible transcription factors, in which the p65/p50 heterodimer is the most abundant complex, that play critical roles mainly in inflammation. Glucocorticoid Receptor (GR) is a ligand-activated transcription factor and acts as an anti-inflammatory agent and immunosuppressant. Thus, NF-kB and GR are physiological antagonists in the inflammation process. Here we show that in mice and humans there is a spliced variant of p65, named p65 iso5, which binds the corticosteroid hormone dexamethasone amplifying the effect of the glucocorticoid receptor and is expressed in the liver of patients with hepatic cirrhosis and hepatocellular carcinoma (HCC). Furthermore, we have quantified the gene expression level of p65 and p65 iso5 in the PBMC of patients affected by SARS-CoV-2 disease. The results showed that in these patients the p65 and p65 iso5 mRNA levels are higher than in healthy subjects. The ability of p65 iso5 to bind dexamethasone and the regulation of the glucocorticoid (GC) response in the opposite way of the wild type improves our knowledge and understanding of the anti-inflammatory response and identifies it as a new therapeutic target to control inflammation and related diseases.

Correlation between Dexamethasone and miRNAs in the regulation of apoptosis, drug-resistance, and metastasis of cancer cell

: Dexamethasone (Dex) is a synthetic corticosteroid hormone derived from the steroid chemical group and is applicable in treating several pathological conditions like inflammation, autoimmune disease, and malignancies. Recent investigations on the mechanism of action of Dex and its possible interactions with other cellular regulatory networks may help explanation of the inconsistent effects of Dex in cancer treatment. Fine-tuning regulation of essential post-transcriptional regulators such as microRNA (miRNAs) has indispensable impacts on modulating fundamental cellular processes including gene expression, cell proliferation, cell cycling, and apoptosis. Dex appears to act as a double-edged sword on cancer cell progression and metastasis through regulating miRNA networks. As a proof of concept, recent investigations have proved Dex to be effective in cancer-treating either individually or in combination with other therapeutical compounds while several evidences have point to the controversial effects of Dex in the promotion of cancer cell survival, drug-resistance, and metastasis. In addition, it has been proved that other non-coding RNAs (ncRNAs) can also be directly or indirectly affected by Dex. In this review, we aimed to investigate the controversial effect of Dex on the cancer-related miRNAs.

The Relationship Between Diabetes and Depression

Evidence of a bidirectional relationship between depression and diabetes has recently been documented in large prospective studies. Comorbid depression is associated with an increased risk of poor glycemic control, diabetes complications and mortality. Moreover, incident diabetes has also been found to be risk factors for subsequent development of depressive episodes. Furthermore, in a recent systematic review, depression is associated with the subsequent development of T2DM by up to 37% as it causes central obesity, increased release of circulating corticosteroid hormone (which antagonizes the action of insulin) and insulin resistance that is a more common etiological pathway for the development of T2DM. Subsequently, the presence of depression with diabetes has a severe impact for self-care management and long term outcome which includes long term disturbance of mood. Therefore, the purpose of this review is to explain the bidirectional relationship between diabetes and depression and explore the management options that are advocated to enhance the Diabetes self-management education and improve the quality of life for diabetic patients with depression Chatt Maa Shi Hosp Med Coll J; Vol.17 (1); Jan 2018; Page 50-54

Cortisol, Stress and Adaptation during Exercise Training

Cortisol is a corticosteroid hormone produced by the zona fasciculata of the adrenal cortex in the adrenal gland. It plays vital roles in the body’s defense mechanisms when dealing with stress, as well as being important in blood glucose regulation. Regrettably, misconceptions regarding the actions of this hormone have been created around the sports and exercise arena. For example, cortisol most often is viewed as having a counter-productive role in exercise that can lead to a mal-adaptation to the exercise training process, due to the catabolic nature of this hormone with respect to protein turnover. Therefore, the intent of this article is to present an overview and to offer commentary on the necessary and critically important functions of cortisol during exercise, and in the adaptation process associated with exercise training. This is being done to specifically correct several of the misconceptions and misunderstandings that are portrayed within some literature (in particular on the Internet) regarding endocrine responses to exercise and exercise training.Keywords: Endocrine, hormones, glucocorticoids, sports.