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[Selenium and zinc: "antioxidants" for healthy aging?].
Steinbrenner, H, Klotz, LO
Zeitschrift fur Gerontologie und Geriatrie. 2020;(4):295-302
Abstract
Selenium and zinc are essential trace elements and an inadequate dietary intake has been implicated in the decline of immune and cognitive functions in aged persons and in the pathogenesis of age-related disorders. Both micronutrients are often marketed as "antioxidants" in mineral supplements; however, neither selenium nor zinc are antioxidants per se but they may exert beneficial effects as components of enzymes and other proteins that catalyze redox reactions and/or are involved in the maintenance of redox homeostasis. According to epidemiological data older individuals have an increased risk of developing deficiencies in the selenium and zinc status; however, such statistical correlations in epidemiological studies do not imply a causal association. Intervention trials are scarce and have yielded inconsistent and sometimes even adverse results. It should also be noted that the observed deficiencies in micronutrients may not necessarily be attributable to inadequate dietary intake as the absorption and distribution within the body might also be influenced by factors such as medications or interaction with other food ingredients. Thus, any dietary supplementation should be implemented with caution and persons who wish to take mineral supplements should first seek medical advice. This article discusses the role of selenium and zinc in biological antioxidant systems, summarizes findings on the supply and supplementation of aged persons with these trace elements and on the influence they may exert on aging-related health issues, such as cognitive decline and type 2 diabetes mellitus.
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A Guide to Human Zinc Absorption: General Overview and Recent Advances of In Vitro Intestinal Models.
Maares, M, Haase, H
Nutrients. 2020;(3)
Abstract
Zinc absorption in the small intestine is one of the main mechanisms regulating the systemic homeostasis of this essential trace element. This review summarizes the key aspects of human zinc homeostasis and distribution. In particular, current knowledge on human intestinal zinc absorption and the influence of diet-derived factors on bioaccessibility and bioavailability as well as intrinsic luminal and basolateral factors with an impact on zinc uptake are discussed. Their investigation is increasingly performed using in vitro cellular intestinal models, which are continually being refined and keep gaining importance for studying zinc uptake and transport via the human intestinal epithelium. The vast majority of these models is based on the human intestinal cell line Caco-2 in combination with other relevant components of the intestinal epithelium, such as mucin-secreting goblet cells and in vitro digestion models, and applying improved compositions of apical and basolateral media to mimic the in vivo situation as closely as possible. Particular emphasis is placed on summarizing previous applications as well as key results of these models, comparing their results to data obtained in humans, and discussing their advantages and limitations.
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Zinc dysregulation in cancers and its potential as a therapeutic target.
Wang, J, Zhao, H, Xu, Z, Cheng, X
Cancer biology & medicine. 2020;(3):612-625
Abstract
Zinc is an essential element and serves as a structural or catalytic component in many proteins. Two families of transporters are involved in maintaining cellular zinc homeostasis: the ZIP (SLC39A) family that facilitates zinc influx into the cytoplasm, and the ZnT (SLC30A) family that facilitates zinc efflux from the cytoplasm. Zinc dyshomeostasis caused by the dysfunction of zinc transporters can contribute to the initiation or progression of various cancers, including prostate cancer, breast cancer, and pancreatic cancer. In addition, intracellular zinc fluctuations lead to the disturbance of certain signaling pathways involved in the malignant properties of cancer cells. This review briefly summarizes our current understanding of zinc dyshomeostasis in cancer, and discusses the potential roles of zinc or zinc transporters in cancer therapy.
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Zinc Deficiency-An Independent Risk Factor in the Pathogenesis of Haemorrhagic Stroke?
Grüngreiff, K, Gottstein, T, Reinhold, D
Nutrients. 2020;(11)
Abstract
Zinc is an essential trace element for human health and plays a fundamental role in metabolic, immunological and many other biological processes. The effects of zinc are based on the intra- and extracellular regulatory function of the zinc ion (Zn2+) and its interactions with proteins. The regulation of cellular zinc homeostasis takes place via a complex network of metal transporters and buffering systems that react to changes in the availability of zinc in nutrition, chronic diseases, infections and many other processes. Zinc deficiency is associated with impairment of numerous metabolic processes, reduced resistance to infections due to impaired immune functions, changes in skin and its appendages and disorders of wound healing and haemostasis. While ischemic heart attacks (myocardial infarction) occur more frequently with meat-based normal diets, haemorrhagic strokes are more frequently observed with vegetarian/vegan diets. The causes are discussed as deficiencies of various micronutrients, such as vitamin B12, vitamin D, various amino acids and also zinc. In the present review, after a description of the functions of zinc and its resorption, a discussion of daily food intake will follow, with a special focus on the importance of food composition and preparation for the zinc balance. The close interrelationships between proteins, especially albumin and zinc will be discussed. Finally, the possible causes and consequences of a zinc deficiency on the blood vessels and blood coagulation are considered.
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Iron and zinc ions, potent weapons against multidrug-resistant bacteria.
Ye, Q, Chen, W, Huang, H, Tang, Y, Wang, W, Meng, F, Wang, H, Zheng, Y
Applied microbiology and biotechnology. 2020;(12):5213-5227
Abstract
Drug-resistant bacteria are becoming an increasingly widespread problem in the clinical setting. The current pipeline of antibiotics cannot provide satisfactory options for clinicians, which brought increasing attention to the development and application of non-traditional antimicrobial substances as alternatives. Metal ions, such as iron and zinc ions, have been widely applied to inhibit pathogens through different mechanisms, including synergistic action with different metabolic enzymes, regulation of efflux pumps, and inhibition of biofilm formation. Compared with traditional metal oxide nanoparticles, iron oxide nanoparticles (IONPs) and zinc oxide nanoparticles (ZnO-NPs) display stronger bactericidal effect because of their smaller ion particle sizes and higher surface energies. The combined utilization of metal NPs (nanoparticles) and antibiotics paves a new way to enhance antimicrobial efficacy and reduce the incidence of drug resistance. In this review, we summarize the physiological roles and bactericidal mechanisms of iron and zinc ions, present the recent progress in the research on the joint use of metal NPs with different antibiotics, and highlight the promising prospects of metal NPs as antimicrobial agents for tackling multidrug-resistant bacteria.
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Zinc and respiratory tract infections: Perspectives for COVID‑19 (Review).
Skalny, AV, Rink, L, Ajsuvakova, OP, Aschner, M, Gritsenko, VA, Alekseenko, SI, Svistunov, AA, Petrakis, D, Spandidos, DA, Aaseth, J, et al
International journal of molecular medicine. 2020;(1):17-26
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Abstract
In view of the emerging COVID‑19 pandemic caused by SARS‑CoV‑2 virus, the search for potential protective and therapeutic antiviral strategies is of particular and urgent interest. Zinc is known to modulate antiviral and antibacterial immunity and regulate inflammatory response. Despite the lack of clinical data, certain indications suggest that modulation of zinc status may be beneficial in COVID‑19. In vitro experiments demonstrate that Zn2+ possesses antiviral activity through inhibition of SARS‑CoV RNA polymerase. This effect may underlie therapeutic efficiency of chloroquine known to act as zinc ionophore. Indirect evidence also indicates that Zn2+ may decrease the activity of angiotensin‑converting enzyme 2 (ACE2), known to be the receptor for SARS‑CoV‑2. Improved antiviral immunity by zinc may also occur through up‑regulation of interferon α production and increasing its antiviral activity. Zinc possesses anti‑inflammatory activity by inhibiting NF‑κB signaling and modulation of regulatory T‑cell functions that may limit the cytokine storm in COVID‑19. Improved Zn status may also reduce the risk of bacterial co‑infection by improving mucociliary clearance and barrier function of the respiratory epithelium, as well as direct antibacterial effects against S. pneumoniae. Zinc status is also tightly associated with risk factors for severe COVID‑19 including ageing, immune deficiency, obesity, diabetes, and atherosclerosis, since these are known risk groups for zinc deficiency. Therefore, Zn may possess protective effect as preventive and adjuvant therapy of COVID‑19 through reducing inflammation, improvement of mucociliary clearance, prevention of ventilator‑induced lung injury, modulation of antiviral and antibacterial immunity. However, further clinical and experimental studies are required.
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Zinc homeostasis in the secretory pathway in yeast.
Bird, AJ, Wilson, S
Current opinion in chemical biology. 2020;:145-150
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Abstract
It is estimated that up to 10% of proteins in eukaryotes require zinc for their function. Although the majority of these proteins are located in the nucleus and cytosol, a small subset is secreted from cells or is located within an intracellular compartment. As many of these compartmentalized metalloproteins fold to their native state and bind their zinc cofactor inside an organelle, cells require mechanisms to maintain supply of zinc to these compartments even under conditions of zinc deficiency. At the same time, intracellular compartments can also be the site for storing zinc ions, which then can be mobilized when needed. In this review, we highlight insight that has been obtained from yeast models about how zinc homeostasis is maintained in the secretory pathway and vacuole.
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Japan's Practical Guidelines for Zinc Deficiency with a Particular Focus on Taste Disorders, Inflammatory Bowel Disease, and Liver Cirrhosis.
Kodama, H, Tanaka, M, Naito, Y, Katayama, K, Moriyama, M
International journal of molecular sciences. 2020;(8)
Abstract
Zinc deficiency is common in Japan, yet awareness on this disorder is lacking. The Japanese Society of Clinical Nutrition recently issued the Japan's Practical Guideline for Zinc Deficiency 2018 setting forth criteria for diagnosing zinc deficiency, i.e., (a) one or more symptoms of zinc deficiency or low serum alkaline phosphatase, (b) ruling out other diseases, (c) low serum zinc, and (d) alleviation of symptoms upon zinc administration. Serum zinc <60 μg/dL and 60-80 μg/dL indicate zinc deficiency and marginal deficiency, respectively. Zinc deficiency symptoms vary and include dermatitis and taste disorders among others. Zinc administration improves taste in 50-82% of patients suffering from taste disorders (a common symptom of zinc deficiency). Effects of zinc administration do not appear immediately, and therapy should be continued for at least three months. Zinc deficiency often accompanies various diseases and conditions. Here, we focus on inflammatory bowel diseases and liver cirrhosis. As zinc deficiency enhances intestinal inflammation via macrophage activation, we discuss the pathological mechanism for inflammation and zinc deficiency in the context of IBD. Zinc deficiency can also lead to a nitrogen metabolic disorder in patients with liver cirrhosis. Zinc supplementation can improve not only the ammonia metabolism, but also the protein metabolism. We also discuss directions for future studies of zinc deficiency.
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Transcription factors and transporters in zinc homeostasis: lessons learned from fungi.
Eide, DJ
Critical reviews in biochemistry and molecular biology. 2020;(1):88-110
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Abstract
Zinc is an essential nutrient for all organisms because this metal serves as a critical structural or catalytic cofactor for many proteins. These zinc-dependent proteins are abundant in the cytosol as well as within organelles of eukaryotic cells such as the nucleus, mitochondria, endoplasmic reticulum, Golgi, and storage compartments such as the fungal vacuole. Therefore, cells need zinc transporters so that they can efficiently take up the metal and move it around within cells. In addition, because zinc levels in the environment can vary drastically, the activity of many of these transporters and other components of zinc homeostasis is regulated at the level of transcription by zinc-responsive transcription factors. Mechanisms of post-transcriptional control are also important for zinc homeostasis. In this review, the focus will be on our current knowledge of zinc transporters and their regulation by zinc-responsive transcription factors and other mechanisms in fungi because these organisms have served as useful paradigms of zinc homeostasis in all organisms. With this foundation, extension to other organisms will be made where warranted.
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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.