Vitamins and Hormones最新文献

Glucose is the primary source of energy for most of the cells and essential for basic functionalities of life's biochemical processes. Transportation of glucose via biological membranes is essential for life mediated by glucose transporters (GLUT) through facilitated diffusion. Glucose transporters perform a crucial role in maintaining normal health as they transfer the most essential molecules of life, glucose. There are 14 various types of glucose transporters that transport primarily glucose and fructose. GUTTs are trans-membrane proteins expressed in the plasma membrane that facilitate the entry of carbohydrate molecules inside the cells. These transporters provide the passage for the carbohydrate molecules, which undergo oxidation inside the cells and provide essential energy in the form of ATPs. Lipid-soluble vitamins, namely A, D, E, and K have been reported to play a key role in stimulating several glucose transporters. Supplementation of lipid-soluble vitamins stimulates the expression of glucose transporters, most importantly GLUT4, GLUT2, GLUT1, and GLUT3, which play a critical role in regulating glucose metabolism in muscle, liver, brain, and RBCs. For their ability to increase the expression of GLUTs, the lipid-soluble vitamins can be the potential micronutrient for combating various non-communicable diseases. The present article discusses the essential role of lipid-soluble vitamins in the regulation of glucose transporters.

In this chapter, we describe a potential new approach to treat lymphoproliferative diseases through isoform-specific knockdown of the long form of the prolactin receptor. The chapter includes a summary of the clinical and experimental links between prolactin and such diseases and presents sufficient background about prolactin and its receptors to explain the rationale for our approach. This background also aims to explain why clinical correlations between circulating prolactin and lymphoproliferative diseases may not appear as great as perhaps they are. In the final sections, we summarize our experimental evidence supporting the use of a splice-modulating oligomer that specifically targets the long form of the prolactin receptor. The work used mouse models of systemic lupus erythematosus and diffuse large B-cell lymphoma, human databases, and normal and malignant human cells. We also refer to previous and current studies using the splice-modulating oligomer which demonstrate its lack of toxicity, including in normal immune cells. For each section, we provide a take-home message in bold font so that the reader has the option to focus briefly or delve into details supporting the take-home message.

Xylose constitutes the second major sugar fraction of the plant-derived lignocellulosic biomass, which is the most abundantly available and renewable feedstock for microbial fermentations. Hence, comprehensive utilization of xylose is crucial from the perspective of sustainable development of bio-based products, such as fuels, fine chemicals, and high-value compounds. Due to several inherent advantages, various species and strains of yeast are employed to produce these biomolecules. With the advancement of genetic engineering in yeast, lignocellulosic biomass has begun to be commercialized for producing various bioproducts required in the food, fuel, pharmaceutical, chemical, and cosmetics industries. The increasing demands of these bioproducts worldwide lead to a necessity of utilizing xylose efficiently for yeast fermentation strategies together with/replacing glucose for more economic sustainability. However, yeast fermentation processes mostly employ glucose; hence, our understanding of xylose utilization by yeast has not been as scrupulous as it should have been. There has been a remarkable increase in the number of studies conducted on xylose utilization and metabolism in yeasts in the past decade. Our objective in this chapter is to highlight the key advancements and novel approaches in this area and to integrate our understanding of xylose metabolism in yeasts, which can help culminate into commercializing strategies in the future for the development of important bioproducts.

Primary aldosteronism (PA) is composed of different aldosterone-producing lesions including aldosterone-producing adenoma (APA), aldosterone-producing micronodules (APM), aldosterone-producing nodules (APN) and aldosterone-producing diffuse hyperplasia (APDH), all of which could result in hypertensive status and electrolyte imbalances. These aldosterone-producing lesions above are frequently accompanied by somatic mutations, including those of KCNJ5, CACNA1D, ATP1A1, and ATP2B3. APA is a neoplasm which frequently harbors KCNJ5 somatic mutations in tumor cells, especially those arising in East Asian patients. Histologically, APAs with KCNJ5 and ATP2B3 mutations presented with more clear cells, whereas those with ATP1A1 and CACNA1D mutations with more compact cells. In addition, the expression levels of steroidogenic enzymes such as aldosterone synthase (CYP11B2) in APAs varied among those with different patterns of somatic mutations, suggesting a potential association between specific mutations and altered aldosterone synthesis in APAs. In contrast, CACNA1D mutation was the most frequent subtype in non-neoplastic lesions including APM and APN, suggesting the possible correlation of KCNJ5 mutation with neoplastic aldosterone-producing lesions. This review provides pivotal insights into the histopathological diversity of aldosterone-producing lesions in PA patients and emphasizes the significance of genetic mutations in constituting the histological landscape of the lesion in order to better understand the detailed pathogenesis of primary aldosteronism.

Steroid Hormone Receptors (SHRs) when bound to its ligand can act as transcription factors, which are responsible for transcription of important genes via hormone responsive element in our genome. Many studies have revealed the molecular mechanisms involved with SHRs. Cancer specific aberrant expression pattern of SHR and variation in their mechanism created an opportunity to specifically target SHRs for developing highly effective anti-cancer therapeutics. Further, these receptors can be targeted using different nanodelivery systems thus proving to be a potent target. The anticancer nanodelivery system can selectively target cancer cells due to the newly discovered aberrant nature of SHRs in cancer making it unique from other membrane bound receptors that are relatively more easily accessible as these are mostly overexpressed on the surface of the cells. One such interesting receptor which is present in the cytoplasm of the cells and ubiquitously expressed in both cancer and non-cancer cells is glucocorticoid receptor (GR). GR as studied earlier behaves in a unique way in cancer cells which facilitates the nanodelivery system including small molecules to selectively target cytoplasmic GR and hence makes the anticancer therapeutics more precise in its own way. Here, we will summarize the knowledge of SHR providing information about its role in its molecular mechanisms in cells and mostly to dig into its anticancer therapeutic roles in cancer cells. Most importantly how the lipid nanoformulation can modulate the SHRs ligand binding domain in cancer therapeutics is also discussed. This also deals with all the SHRs including estrogen, progesterone, mineralocorticoid receptors and androgen receptors.

In fat and skeletal muscle cells, insulin causes plasma membrane translocation of specialized insulin-responsive vesicles, or IRVs. These vesicles consist of multiple copies of Glut4, sortilin, IRAP, and LRP1 as well as several auxiliary components. Major IRV proteins have relatively long half-life inside the cell and survive multiple rounds of translocation to and from the cell surface. Here, we summarize evidence showing how the IRVs are self-assembled from pre-synthesized Glut4, sortilin, IRAP, and LRP1 after each translocation event. Furthermore, the cytoplasmic tail of sortilin binds Akt while cytoplasmic tails of IRAP and LRP1 interact with the Akt target, TBC1D4. Recruitment of signaling proteins to the IRVs may render insulin responsiveness to this compartment and thus distinguish it from other intracellular membrane vesicles.

The balance between food intake and energy expenditure is precisely regulated to maintain adipose stores. Leptin, which is produced in and released from adipose in direct proportion to its size, is a major contributor to this control and initiates its homeostatic responses largely via binding to leptin receptors (LepR) in the hypothalamus. Decreases in hypothalamic LepR binding signals starvation, leading to hunger and reduced energy expenditure, whereas increases in hypothalamic LepR binding can suppress food intake and increase energy expenditure. However, large gaps persist in the specific hypothalamic sites and detailed mechanisms by which leptin increases energy expenditure, via the parallel activation of the hypothalamic pituitary thyroid (HPT) axis and brown adipose tissue (BAT). The purpose of this review is to develop a framework for the complex mechanisms and neurocircuitry. The core circuitry begins with leptin binding to receptors in the arcuate nucleus, which then sends projections to the paraventricular nucleus (to regulate the HPT axis) and the dorsomedial hypothalamus (to regulate BAT). We build on this core by layering complexities, including the intricate and unsettled regulation of arcuate proopiomelanocortin neurons by leptin and the changes that occur as the regulation of the HPT axis and BAT is engaged or modified by challenges such as starvation, hypothermia, obesity, and pregnancy.

Iron is an essential trace element that plays a crucial role in various biological processes, including oxygen transport, DNA synthesis and cell proliferation. Iron homeostasis is a critical biological equilibrium that involves the balance of iron absorption, utilization, storage and excretion. Iron is intricately linked to the pathophysiology of cancer. Its dual role as a vital nutrient and a potential carcinogen highlights the complexity of iron's influence on tumorigenesis. Iron balance is finely tuned through a complex interplay of molecular components and regulatory mechanisms. Hepcidin, a liver-derived peptide hormone, is the principal regulator of systemic iron availability. Hepcidin exerts its effects by binding to the iron export protein ferroportin (FPN1), leading to its internalization and degradation, which in turn reduces the release of iron from macrophages and the intestinal absorption of dietary iron. In human cancers, the expression of hepcidin is significantly altered, leading to increased iron absorption and retention. Hepcidin has emerged as a significant player in cancer biology due to its potential as both a tumor suppressor and a promoter. Understanding the context-dependent role of hepcidin in cancer opens avenues for novel therapeutic strategies. Modulating hepcidin levels or its activity could be a potential approach to treat cancer, either by starving tumors of iron or by normalizing the iron-rich microenvironment to enhance the efficacy of existing cancer treatments. In this review, we provide a comprehensive overview of the critical functions of hepcidin in iron metabolism, summarize the upstream regulatory factors that control the expression of hepcidin, and delve deeply into the downstream signaling pathways and molecular mechanisms by which hepcidin regulates the tumorigenesis, as well as elucidate the promising potential of hepcidin as a novel therapeutic target in the treatment of cancer, underscoring the significance of understanding and harnessing the complex interplay between hepcidin, iron metabolism and cancer biology.