Vitamins and Hormones最新文献

Naturally occurring forms of vitamin B6 include six interconvertible water-soluble compounds: pyridoxine (PN), pyridoxal (PL), pyridoxamine (PM), and their respective monophosphorylated derivatives (PNP, PLP, and PMP). PLP is the catalytically active form which works as a cofactor in approximately 200 reactions that regulate the metabolism of glucose, lipids, amino acids, DNA, and neurotransmitters. Most of vitamers can counteract the formation of reactive oxygen species and the advanced glycation end-products (AGEs) which are toxic compounds that accumulate in diabetic patients due to prolonged hyperglycemia. Vitamin B6 levels have been inversely associate with diabetes, while vitamin B6 supplementation reduces diabetes onset and its vascular complications. The mechanisms at the basis of the relation between vitamin B6 and diabetes onset are still not completely clarified. In contrast more evidence indicates that vitamin B6 can protect from diabetes complications through its role as scavenger of AGEs. It has been demonstrated that in diabetes AGEs can destroy the functionality of macromolecules such as protein, lipids, and DNA, thus producing tissue damage that result in vascular diseases. AGEs can be in part also responsible for the increased cancer risk associated with diabetes. In this chapter the relationship between vitamin B6, diabetes and AGEs will be discussed by showing the acquired knowledge and questions that are still open.

Advanced glycation end products (AGEs) are formed by the non-enzymatic attachment of carbohydrates to a biological macromolecule. These AGEs bind to their cognate receptor called receptor for AGEs (RAGEs), which becomes one of the important causal factors for the initiation and progression of several diseases. A deep understanding into the pathways of RAGEs will help in identifying novel intervention modalities as a part of new therapeutic strategies. Although several approaches exist to target this pathway using small molecules, compounds of plant origin etc, nanoparticles have proven to be a critical method, given its several advantages. A high bioavailability, biocompatibility, ability to cross blood brain barrier and modifiable surface properties give nanoparticles an upper edge over other strategies. In this chapter, we will discuss AGEs, their involvement in diseases and the nanoparticles used for targeting this pathway.

The century old Maillard reactions continue to draw the interest of researchers in the fields of Food Science and Technology, and Health and Medical Sciences. This chapter seeks to simplify and update this highly complicated, multifaceted topic. The simple nucleophilic attack of an amine onto a carbonyl group gives rise to a series of parallel and subsequent reactions, occurring simultaneously, resulting into a vast array of low and high mass compounds. Recent research has focused on: (1) the formation and transformation of α-dicarbonyl compounds, highly reactive intermediates which are essential in the development of the desired color and flavor of foods, but also lead to the production of the detrimental advanced glycation end products (AGEs); (2) elucidation of the structures of melanoidins in different foods and their beneficial effects on human health; and (3) harmful effects of AGEs on human health. Considering that MRs have both positive and negative consequences, their control to accentuate the former and to mitigate the latter, is also being conscientiously investigated with the use of modern techniques and technology.

The blood-brain barrier (BBB) is a unique system of the brain microvasculature that limits the exchange between the blood and the brain. Brain microvascular endothelial cells form the BBB as part of the neurovascular unit and express insulin receptors. The insulin receptor at the BBB has been studied in two different functional aspects. These functions include (1) the supplying of blood insulin to the brain and (2) the modulation of BBB function via insulin signaling. The first function involves drug delivery to the brain, while the second function is related to the association between central nervous system diseases and type 2 diabetes through insulin resistance. This chapter summarizes recent progress in research on the function of insulin receptors at the BBB.

Sleep is a physiological process that preserves the integrity of the neuro-immune-endocrine network to maintain homeostasis. Sleep regulates the production and secretion of hormones, neurotransmitters, cytokines and other inflammatory mediators, both at the central nervous system (CNS) and at the periphery. Sleep promotes the removal of potentially toxic metabolites out of the brain through specialized systems such as the glymphatic system, as well as the expression of specific transporters in the blood-brain barrier. The blood-brain barrier maintains CNS homeostasis by selectively transporting metabolic substrates and nutrients into the brain, by regulating the efflux of metabolic waste products, and maintaining bidirectional communication between the periphery and the CNS. All those processes are disrupted during sleep loss. Brain endothelial cells express the blood-brain barrier phenotype, which arises after cell-to-cell interactions with mural cells, like pericytes, and after the release of soluble factors by astroglial endfeet. Astroglia, pericytes and brain endothelial cells respond differently to sleep loss; evidence has shown that sleep loss induces a chronic low-grade inflammatory state at the CNS, which is associated with blood-brain barrier dysfunction. In animal models, blood-brain barrier dysfunction is characterized by increased blood-brain barrier permeability, decreased tight junction protein expression and pericyte detachment from the capillary wall. Blood-brain barrier dysfunction may promote defects in brain clearance of potentially neurotoxic metabolites and byproducts of neural physiology, which may eventually contribute to neurodegenerative diseases. This chapter aims to describe the cellular and molecular mechanisms by which sleep loss modifies the function of the blood-brain barrier.

The blood-brain barrier (BBB) is a highly selective membrane that regulates the passage of substances between the bloodstream and the brain, thus safeguarding the central nervous system. This chapter provides an overview of current experimental models and detection methods utilized to study the BBB, along with the implementation of sensors and biosensors in BBB research. We discuss static and dynamic BBB models, highlighting their respective advantages and limitations. Additionally, we examine various detection methods employed in BBB research, including those specific to static and dynamic models. Furthermore, we explore the applications of physical sensors and biosensors in BBB models, focusing on their roles in monitoring barrier integrity and function. We also discuss recent advancements in sensor integration, such as robotic interrogators and integrated electrochemical and optical biosensors. Finally, we present a brief conclusion and future outlook, emphasizing the importance of continued innovation in BBB research to advance our understanding of neurological disorders and drug development.

This article discusses the physiological and anatomical changes of adrenal gland with age and the effects this has overall on how the organ responds to stress. Physiological changes entail a decrease in adrenocorticoid hormone secretion however cortisol levels remain intact leading to a disruptive stress response. Additionally, loss of zonation of the organ also occurs. Both characteristics in combination with chronic stress affect overall health. Complex interplay between adrenal aging and stress responsiveness is confounded further by the impact they expel on other systems, such as the thyroid hormone. The body undergoes age-related transformations modifying rate of cellular growth, differentiation, senescence, and hormone production. Given the multiplicity and complexity of hormones, their production must be considered to develop appropriate interventions to mitigate its effect on age related diseases in health.

The adrenal cortex is responsible for production of adrenal steroid hormones and is anatomically divided into three distinct zones: zona glomerulosa secreting mineralocorticoids (mainly aldosterone), zona fasciculata secreting glucocorticoids (cortisol), and zona reticularis producing androgens. Importantly, due to their high lipophilicity, no adrenal steroid hormone (including aldosterone) is stored in vesicles but rather gets synthesized and secreted instantly upon cell stimulation with specific stimuli. Aldosterone is the most potent mineralocorticoid hormone produced from the adrenal cortex in response to either angiotensin II (AngII) or elevated K⁺ levels in the blood (hyperkalemia). AngII, being a peptide, cannot cross cell membranes and thus, uses two distinct G protein-coupled receptor (GPCR) types, AngII type 1 receptor (AT₁R) and AT₂R to exert its effects inside cells. In zona glomerulosa cells, AT₁R activation by AngII results in aldosterone synthesis and secretion via two main pathways: (a) G_q/11 proteins that activate phospholipase C ultimately raising intracellular free calcium concentration; and (b) βarrestin1 and -2 (also known as Arrestin-2 and -3, respectively) that elicit sustained extracellular signal-regulated kinase (ERK) activation. Both pathways induce upregulation and acute activation of StAR (steroidogenic acute regulatory) protein, the enzyme that catalyzes the rate-limiting step in aldosterone biosynthesis. This chapter describes these two salient pathways underlying AT₁R-induced aldosterone production in zona glomerulosa cells. We also highlight some pharmacologically important notions pertaining to the efficacy of the currently available AT₁R antagonists, also known as angiotensin receptor blockers (ARBs) or sartans at suppressing both pathways, i.e., their inverse agonism efficacy at G proteins and βarrestins.

Although renin-angiotensin-aldosterone system (RAAS) is known to maintain blood pressure and electrolyte balance, it has recently been linked to a number of biological processes such as angiogenesis, tumorigenesis, metastasis, and cellular proliferation, increasing the risk of cancer development and progression. Multiple genetic variants have been found to affect the genes encoding RAAS components, altering gene transcription and protein expression. This review provides an up-to-date insight into the role of RAAS in carcinogenesis, as well as the impact of RAAS genetic variants on the risk of cancer development, progression, and patient survival and outcomes, as well as response to treatment. This paves the way for the application of precision medicine in cancer risk assessment and management by implementing preventative programs in individuals at risk and guiding the therapeutic direction in cancer patients.

Brain microvascular endothelial cells, which lie at the interface between blood and brain, are critical to brain energetics. These cells must precisely balance metabolizing nutrients for their own demands with transporting nutrients into the brain to sustain parenchymal cells. It is essential to understand this integrated metabolism and transport so that we can develop better diagnostics and therapeutics for neurodegenerative diseases such as Alzheimer's disease, multiple sclerosis, and traumatic brain injury. In this chapter, we first describe brain microvascular endothelial cell metabolism and how these cells regulate both blood flow and nutrient transport. We then explain the impact of brain microvascular endothelial cell metabolism on the integrity of the blood-brain barrier, as well as how metabolites produced by the endothelial cells impact other brain cells. We detail some ways that cell metabolism is typically measured experimentally and modeled computationally. Finally, we describe changes in brain microvascular endothelial cell metabolism in aging and neurodegenerative diseases. At the end of the chapter, we highlight areas for future research in brain microvascular endothelial cell metabolism. The goal of this chapter is to underscore the importance of nutrient metabolism and transport at the brain endothelium for cerebral health and neurovascular disease treatment.