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Harnessing Metal Homeostasis Offers Novel and Promising Targets Against Candida albicans.
Hameed, S, Hans, S, Singh, S, Fatima, Z
Current drug discovery technologies. 2020;(4):415-429
Abstract
Fungal infections, particularly of Candida species, which are the commensal organisms of human, are one of the major debilitating diseases in immunocompromised patients. The limited number of antifungal drugs available to treat Candida infections, with the concomitant increasing incidence of multidrug-resistant (MDR) strains, further worsens the therapeutic options. Thus, there is an urgent need for the better understanding of MDR mechanisms, and their reversal, by employing new strategies to increase the efficacy and safety profiles of currently used therapies against the most prevalent human fungal pathogen, Candida albicans. Micronutrient availability during C. albicans infection is regarded as a critical factor that influences the progression and magnitude of the disease. Intracellular pathogens colonize a variety of anatomical locations that are likely to be scarce in micronutrients, as a defense strategy adopted by the host, known as nutritional immunity. Indispensable critical micronutrients are required both by the host and by C. albicans, especially as a cofactor in important metabolic functions. Since these micronutrients are not freely available, C. albicans need to exploit host reservoirs to adapt within the host for survival. The ability of pathogenic organisms, including C. albicans, to sense and adapt to limited micronutrients in the hostile environment is essential for survival and confers the basis of its success as a pathogen. This review describes that micronutrients availability to C. albicans is a key attribute that may be exploited when one considers designing strategies aimed at disrupting MDR in this pathogenic fungi. Here, we discuss recent advances that have been made in our understanding of fungal micronutrient acquisition and explore the probable pathways that may be utilized as targets.
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Inadequacy of Immune Health Nutrients: Intakes in US Adults, the 2005-2016 NHANES.
Reider, CA, Chung, RY, Devarshi, PP, Grant, RW, Hazels Mitmesser, S
Nutrients. 2020;(6)
Abstract
A well-functioning immune system is essential for human health and well-being. Micronutrients such as vitamins A, C, D, E, and zinc have several functions throughout the immune system, yet inadequate nutrient intakes are pervasive in the US population. A large body of research shows that nutrient inadequacies can impair immune function and weaken the immune response. Here, we present a new analysis of micronutrient usual intake estimates based on nationally representative data in 26,282 adults (>19 years) from the 2005-2016 National Health and Nutrition Examination Surveys (NHANES). Overall, the prevalence of inadequacy (% of population below estimated average requirement [EAR]) in four out of five key immune nutrients is substantial. Specifically, 45% of the U.S. population had a prevalence of inadequacy for vitamin A, 46% for vitamin C, 95% for vitamin D, 84% for vitamin E, and 15% for zinc. Dietary supplements can help address nutrient inadequacy for these immune-support nutrients, demonstrated by a lower prevalence of individuals below the EAR. Given the long-term presence and widening of nutrient gaps in the U.S.-specifically in critical nutrients that support immune health-public health measures should adopt guidelines to ensure an adequate intake of these micronutrients. Future research is needed to better understand the interactions and complexities of multiple nutrient shortfalls on immune health and assess and identify optimal levels of intake in at-risk populations.
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3.
Micronutrients as immunomodulatory tools for COVID-19 management.
Gasmi, A, Tippairote, T, Mujawdiya, PK, Peana, M, Menzel, A, Dadar, M, Gasmi Benahmed, A, Bjørklund, G
Clinical immunology (Orlando, Fla.). 2020;:108545
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Abstract
COVID-19 rapidly turned to a global pandemic posing lethal threats to overwhelming health care capabilities, despite its relatively low mortality rate. The clinical respiratory symptoms include dry cough, fever, anosmia, breathing difficulties, and subsequent respiratory failure. No known cure is available for COVID-19. Apart from the anti-viral strategy, the supports of immune effectors and modulation of immunosuppressive mechanisms is the rationale immunomodulation approach in COVID-19 management. Diet and nutrition are essential for healthy immunity. However, a group of micronutrients plays a dominant role in immunomodulation. The deficiency of most nutrients increases the individual susceptibility to virus infection with a tendency for severe clinical presentation. Despite a shred of evidence, the supplementation of a single nutrient is not promising in the general population. Individuals at high-risk for specific nutrient deficiencies likely benefit from supplementation. The individual dietary and nutritional status assessments are critical for determining the comprehensive actions in COVID-19.
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4.
Vitamin D: A Micronutrient Regulating Genes.
Carlberg, C
Current pharmaceutical design. 2019;(15):1740-1746
Abstract
BACKGROUND At sufficient sun exposure, humans can synthesize vitamin D3 endogenously in their skin, but today's lifestyle makes the secosteroid a true vitamin that needs to be taken up by diet or supplementation with pills. The vitamin D3 metabolite 1α,25-dihydroxyvitamin D3 acts as a nuclear hormone activating the transcription factor vitamin D receptor (VDR). METHODS This review discusses the biological effects of micronutrient vitamin D ranging from calcium homeostasis and bone formation to the modulation of innate and adaptive immunity. RESULTS Since normal human diet is sufficient in vitamin D, the need for efficient vitamin D3 synthesis in the skin acts as an evolutionary driver for its lightening during the migration out of Africa towards North. Via activating the VDR, vitamin D has direct effects on the epigenome and the expression of more than 1000 genes in most human tissues and cell types. CONCLUSIONS The pleiotropic action of vitamin D in health and disease prevention is explained through complex gene regulatory events of the transcription factor VDR.
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Micronutrient Absorption and Related Outcomes in People with Inflammatory Bowel Disease: A Review.
Kilby, K, Mathias, H, Boisvenue, L, Heisler, C, Jones, JL
Nutrients. 2019;(6)
Abstract
Inflammatory Bowel Disease (IBD) is a chronic disorder associated with immune dysregulation and chronic inflammation of the digestive tract. While it is poorly understood, the role of nutrition and nutrient status in the etiology of IBD and its associated outcomes has led to increased research relating to micronutrient deficiency. This review offers an overview of recent literature related to micronutrient absorption and outcomes in adults with IBD. Although the absorption and IBD-related outcomes of some micronutrients (e.g., vitamin D and iron) are well understood, other micronutrients (e.g., vitamin A) require further research. Increased research and clinician knowledge of the relationship between micronutrients and IBD may manifest in improved nutrient screening, monitoring, treatment, and outcomes for people living with IBD.
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Micronutrient deficiencies in patients with chronic atrophic autoimmune gastritis: A review.
Cavalcoli, F, Zilli, A, Conte, D, Massironi, S
World journal of gastroenterology. 2017;(4):563-572
Abstract
Chronic atrophic autoimmune gastritis (CAAG) is an organ-specific autoimmune disease characterized by an immune response, which is directed towards the parietal cells and intrinsic factor of the gastric body and fundus and leads to hypochlorhydria, hypergastrinemia and inadequate production of the intrinsic factor. As a result, the stomach's secretion of essential substances, such as hydrochloric acid and intrinsic factor, is reduced, leading to digestive impairments. The most common is vitamin B12 deficiency, which results in a megaloblastic anemia and iron malabsorption, leading to iron deficiency anemia. However, in the last years the deficiency of several other vitamins and micronutrients, such as vitamin C, vitamin D, folic acid and calcium, has been increasingly described in patients with CAAG. In addition the occurrence of multiple vitamin deficiencies may lead to severe hematological, neurological and skeletal manifestations in CAAG patients and highlights the importance of an integrated evaluation of these patients. Nevertheless, the nutritional deficiencies in CAAG are largely understudied. We have investigated the frequency and associated features of nutritional deficiencies in CAAG in order to focus on any deficit that may be clinically significant, but relatively easy to correct. This descriptive review updates and summarizes the literature on different nutrient deficiencies in CAAG in order to optimize the treatment and the follow-up of patients affected with CAAG.
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Small and Hungry: MicroRNAs in Micronutrient Homeostasis of Plants.
Patel, P, Yadav, K, Ganapathi, TR
MicroRNA (Shariqah, United Arab Emirates). 2017;(1):22-41
Abstract
MicroRNAs are emerging players in plant development and response to stresses, both biotic and abiotic such as micronutrient deficiency. These small RNAs regulate cognate downstream targets either by transcript cleavage or translational inhibition. Micronutrient deficiencies lead to poor quality and yield of crops and impaired human health. Over the years several microRNAs have been identified which regulate expression of genes controlling uptake, mobilization and homeostasis of macronutrients such as nitrogen, phosphorus and sulfur to ensure sufficiency without toxicity. This review attempts to understand the roles played by micro RNAs involved in homeostasis of the micronutrients boron, manganese, zinc, copper, iron, molybdenum and nickel and the cross talk between them upon perception of nutritional stress. Notably and surprisingly, several micro RNAs are not specific for a particular micronutrient stress and the challenge remains to uncover ones (if any) that are directly relevant to the micronutrient. Current findings of this yet infant field could potentiate biotechnological applications towards biofortification, plant innate immunity and remedy heavy metal toxicity.