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Topic review
Updated time: 07 Jan 2021
Submitted by: Mark Evans
Definition: We live and to do so we must breathe and eat, so are we a combination of what we eat and breathe? Here we will consider this question, and the role in this respect of the AMP-activated protein kinase (AMPK). Emerging evidence suggests that AMPK facilitates central and peripheral reflexes that coordinate breathing and oxygen supply, and contributes to central regulation of feeding and food choice. We propose, therefore, that oxygen supply to the body is aligned with not only the quantity we eat, but also nutrient-based diet selection, and that the cell-specific expression pattern of AMPK subunit isoforms is critical to appropriate system alignment in this respect. If this is the case, then aberrant cell-specific changes in the expression of AMPK subunit isoforms could give rise, in part, to known associations between a wide variety of conditions associated with metabolic disorder.
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Topic review
Updated time: 15 Jan 2021
Submitted by: Markéta Šimková
Definition: Androgens represent the main hormones responsible for maintaining hormonal balance and function in the prostate and testis. As they are involved in prostate and testicular carcinogenesis, more detailed information of their active concentration at the site of action is required. Since the introduction of the term intracrinology as the local formation of active steroid hormones from inactive precursors of the adrenal gland, mainly dehydroepiandrosterone (DHEA) and DHEA-S, it is evident that blood circulating levels of sex steroid hormones need not reflect their actual concentrations in the tissue.
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Topic review
Updated time: 07 Jul 2020
Submitted by: Amanda St Paul
Definition: Cardiovascular disease is the leading cause of morbidity and mortality in the western and developing world, and the incidence of cardiovascular disease is increasing with the longer lifespan afforded by our modern lifestyle. Vascular diseases including coronary heart disease, high blood pressure, and stroke comprise the majority of cardiovascular disease and therefore represent a significant medical and socioeconomic burden on our society. It is not be surprising that these conditions overlap and potentiate each other when we consider the many cellular and molecular similarities between them. At the molecular level, the vascular smooth muscle cell (VSMC) is the target, integrator, and effector cell of both atherogenic and the major effector protein of the hypertensive signal, Angiotensin II (Ang II). Together, these signals can potentiate each other and prime the artery and exacerbate hypertension and atherosclerosis. Therefore, VSMC are the fulcrum in progression of these diseases and therefore, understanding the effects of atherogenic stimuli and Ang II on VSMC is key to understanding and treating atherosclerosis and hypertension. In this review, we will examine studies in which hypertension and atherosclerosis intersect on the VSMC, and illustrate common pathways between these two diseases and vascular aging.
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Topic review
Updated time: 08 Feb 2021
Submitted by: Jayarama Gunaje
Definition: Aspirin is a non-steroidal anti-inflammatory drug that is routinely used in decreasing inflammation, pain, fever and cardiovascular diseases. Aspirin has recently been recommended for the prevention of colorectal cancers (CRC) in adults aged above 59 yrs by the United States Preventive Services Task Force (USPSTF). Though acknowledged for its ability to decrease incidences of CRC, a consensus has not yet been reached regarding the mechanisms involved in its chemopreventive actions. Here, we briefly describe the "metabolite hypothesis", discuss its strengths and limitations and provide our perspective.
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Topic review
Updated time: 27 Mar 2021
Submitted by: Jan Jakubík
Definition: G-protein coupled receptors (GPCRs) are membrane proteins that convey extracellular signals to the cellular milieu. They represent a target for more than 30% of currently marketed drugs.
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Topic review
Updated time: 05 Nov 2020
Definition: Cholesterol, the most important sterol in mammals, helps maintain plasma membrane fluidity and is a precursor of bile acids, oxysterols, and steroid hormones. Cholesterol in the body is obtained from the diet or can be de novo synthetized. Cholesterol homeostasis is mainly regulated by the liver, where cholesterol is packed in lipoproteins for transport through a tightly regulated process. Changes in circulating lipoprotein cholesterol levels lead to atherosclerosis development, which is initiated by an accumulation of modified lipoproteins in the subendothelial space; this induces significant changes in immune cell differentiation and function. In this entry, we describe the main regulatory pathways and mechanisms of cholesterol metabolism.
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Topic review
Updated time: 02 Feb 2021
Submitted by: MARY ANNA VENNERI
Definition: Infertility represents a growing health problem in industrialized countries. Thus, a greater understanding of the molecular networks involved in this disease could be critical for the development of new therapies. A recent finding revealed that circadian rhythmicity disruption is one of the main causes of poor reproductive outcome. The circadian clock system beats circadian rhythms and modulates several physiological functions such as the sleep-wake cycle, body temperature, heart rate, and hormones secretion, all of which enable the body to function in response to a 24 h cycle. This intricated machinery is driven by specific genes, called “clock genes” that fine-tune body homeostasis. Stress of modern lifestyle can determine changes in hormone secretion, favoring the onset of infertility-related conditions that might reflect disfunctions within the hypothalamic–pituitary–gonadal axis. Consequently, the loss of rhythmicity in the suprachiasmatic nuclei might affect pulsatile sexual hormones release. Herein, we provide an overview of the recent findings, in both animal models and humans, about how fertility is influenced by circadian rhythm. In addition, we explore the complex interaction among hormones, fertility and the circadian clock. A deeper analysis of these interactions might lead to novel insights that could ameliorate the therapeutic management of infertility and related disorders.
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Topic review
Updated time: 29 Oct 2020
Submitted by: Angelos Sikalidis
Definition: Sarcopenia develops over time as a result of aging, and typically leads to muscle loss, a concurrent increase in fat mass, and a variety of health issues leading to an overall poor quality of life. There is some evidence that sarcopenia may be a contributing to the development of type 2 diabetes mellitus (T2DM) in the elderly, and therefore nutritional management is key in the prevention of both sarcopenia and T2DM. The primary focus of nutritional management lays in the amount and quality of protein intake, which has led to the development of clinical nutritional therapies involving amino acids to improve muscle protein synthesis and decrease sarcopenia symptoms. In the work herein, we present and evaluate data derived from human trials regarding the utilization of hydroxyl-methyl butyrate (HMB), L-leucine (Leu), L-glutamine (Gln) and L-arginine (Arg) supplementation for optimal management of sarcopenia in geriatric patients, a topic of significant clinical nutrition interest which may have important implications in T2DM management.
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Topic review
Updated time: 19 Feb 2021
Submitted by: Silvano Bertelloni
Definition: Complete androgen insensitivity syndrome (CAIS) is due to complete resistance to the action of androgens, determining a female phenotype in persons with a 46,XY karyotype and functioning testes.
Topic review
Updated time: 14 Jul 2020
Submitted by: Hannu Raunio
Definition: Activities of xenobiotic-metabolizing enzymes have been measured with various in vitro and in vivo methods, such as spectrophotometric, fluorometric, mass spectrometric and radioactivity-based techniques. In fluorescence-based assays, the reaction produces a fluorescent product from a nonfluorescent substrate or vice versa. We describe here historical highlights and current use of (pro)fluorescent coumarin derivatives in evaluating activities of the major types of xenobiotic-metabolizing enzyme systems. Traditionally coumarin substrates have been used to measure oxidative activities of cytochrome P450 (CYP) enzymes. For this purpose, profluorescent coumarins are very sensitive, but generally lack selectivity for individual CYP forms. The entry describes several new coumarin-based substrates for measuring activities of CYP and conjugating enzymes with improved selectivity.
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