Vitamins and Hormones最新文献

Breast cancer is a widely prevalent and devastating morbidity that affects millions of women around the world. Conventional treatment options for breast cancer include surgery, chemotherapy, and radiotherapy. However, these therapies can frequently have adverse side effects and may not be effective for all patients. In recent years, there has been an increasing interest in the development of targeted therapies for breast cancer. Glut-1, a key glucose transporter that is often overexpressed in breast cancer cells, is a potential candidate for targeted therapies. Glut-1 is crucial for basal glucose transport into cancer cells and is necessary for their rapid growth and survival. Several Glut-1 inhibitors - both natural and synthetic small molecules - have been identified and used as anticancer agents. In this chapter, we summarize the different approaches of Glut-1 inhibition in breast cancer and the mode of inhibition used by various Glut-1 inhibitors. Further understanding of the mechanisms underlying the efficacy of Glut-1 inhibitors in breast cancer treatment may provide crucial insights that can lead to the advancement of current treatment strategies. The functional inhibition of Glut-1 by specific Glut-1 inhibitors is being explored as a potential treatment modality for breast cancer. This approach holds great promise for improving the therapeutic efficacy of breast cancer treatment and minimizing the side effects associated with conventional therapies.

The hypothalamus is one of the most complex region in the central nervous system regarding neuroanatomy, neurochemical content, neuropeptide/classical neurotransmitter interactions, physiological actions, and pathophysiology. Hypothalamic neuropeptides have been involved in a large plethora of mechanisms related with obesity, anxiety, feeding, energy metabolism, defensive behavior, mood, and reproduction. The therapeutic potential of these findings is enormous but the physiological complexity occurring in the hypothalamus is huge due in part to the interactions between numerous neuropeptides as well as between neuropeptides and other neuroactive substances. Here, we review the development and neuroanatomy of the hypothalamus as well as the involvement of 31 neuropeptides in hypothalamic functions and pathologies. Alterations in the secretion, release, and/or concentrations of neuropeptides and/or their hypothalamic receptors can trigger different pathologies. Several therapeutic strategies that could be carried out by adjusting neuropeptide levels in the hypothalamus are suggested. The combination of imaging techniques with a detailed neurochemical knowledge of the hypothalamus would be an excellent diagnostic tool, allowing personalized treatment. Several approaches for future research that may contribute to improve or resolve these pathologies are also mentioned.

FDA approval of selective CDK4/6 inhibitors (CDK4/6i) marked a groundbreaking development in cancer treatment. Decades of pre-clinical studies elucidated the route that certain cancer cells take to gain the cancer hallmark of uncontrolled proliferation, uncovering CDK4/6 as key players. Further investigation into the molecular underpinnings of this process revealed interconnected signaling between the CDK4/6 and estrogen receptor (ER) signaling axes, providing evidence that CDK4/6i would be particularly relevant in estrogen-driven cancers. Three FDA-approved CDK4/6 inhibitors, palbociclib, ribociclib, and abemaciclib, were independently developed and all exhibited efficacy against in vivo models of ER+ breast cancer. Clinical trials then confirmed the safety and efficacy of these drugs in patients. Ongoing clinical trials are now testing CDK4/6i in several other cancer models, including other hormone-driven cancers. Further mechanistic insights should reveal predictive biomarkers of response, and potential combination therapies to overcome resistance. This chapter provides an overview of the development of these drugs, their current utility, and their potential use in the treatment of multiple malignancies.

The hypothalamus is the gray matter of the ventral portion of the diencephalon. The hypothalamus is the higher center of the autonomic nervous system and is involved in the regulation of various homeostatic mechanisms. It also modulates respiration by facilitating the respiratory network. Among subregions of the hypothalamus, the paraventricular nucleus, lateral hypothalamic area, perifornical area, dorsomedial and posterior hypothalamus play particularly important roles in respiratory control. Neurons in these regions have extensive and complex interconnectivity with the cerebral cortex, pons, medulla, spinal cord, and other brain areas. These hypothalamic regions are involved in the maintenance of basal ventilation, respiratory responses to hypoxic and hypercapnic conditions, respiratory augmentation during dynamic exercise, and respiratory modulation in awake and sleep states. Disorders affecting the hypothalamus such as narcolepsy, ROHHAD syndrome, and Prader-Willi syndrome could lead to respiratory abnormalities. However, the role of the hypothalamus in respiratory control, especially its interplay with other local respiratory networks has not yet been fully elucidated. Further clarification of these issues would contribute to a better understanding of the hypothalamus-mediated respiratory control and the pathophysiology of respiratory disorders underlain by hypothalamic dysfunction, as well as to the development of new targeted therapies.

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.