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1.
Potential Role of Zinc in the COVID-19 Disease Process and its Probable Impact on Reproduction.
Sethuram, R, Bai, D, Abu-Soud, HM
Reproductive sciences (Thousand Oaks, Calif.). 2022;(1):1-6
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Abstract
COVID-19 (coronavirus disease 2019) is the current world health crisis, producing extensive morbidity and mortality across all age groups. Given the established roles of zinc in combating oxidative damage and viral infections, zinc is being trialed as a treatment modality against COVID-19. Zinc also has confirmed roles in both male and female reproduction. The possible depletion of zinc with the oxidative events of COVID-19 is especially relevant to the fertility of affected couples. This review aims to present the pathophysiology of COVID-19, especially in relation to reproductive function; the role of zinc in the COVID-19 disease process; and how zinc depletion in concert with cytokine storm and reactive oxygen species production could affect reproduction. It also highlights research areas to better the understanding of COVID-19 and its impact on fertility and potential ways to mitigate the impact.
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2.
Medicinal Plants and Zinc: Impact on COVID-19 Pandemic.
Jalal, Z, Bakour, M, Lyoussi, B
TheScientificWorldJournal. 2021;:9632034
Abstract
The world is currently grappling with the coronavirus disease (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The infection can cause fever, a dry cough, fatigue, severe pneumonia, respiratory distress syndrome, and in some cases death. There is currently no effective antiviral SARS-CoV-2 drug. To reduce the number of infections and deaths, it is critical to focus on strengthening immunity. This review aims to conduct a comprehensive search on the previous studies using Google Scholar, ScienceDirect, Medline, PubMed, and Scopus for the collection of research papers based on the role of zinc in the immune system, the antiviral activity of zinc, the effect of zinc supplementation in respiratory infections, the therapeutic approaches against viral infections based on medicinal plants, and the role of plants' bioactive molecules in fighting viral infections. In conclusion, we highlighted the pivotal role of zinc in antiviral immunity and we suggested the bioactive molecules derived from medicinal plants as a search matrix for the development of anti-SARS-CoV-2 drugs.
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Potential molecular mechanisms of zinc- and copper-mediated antiviral activity on COVID-19.
Rani, I, Goyal, A, Bhatnagar, M, Manhas, S, Goel, P, Pal, A, Prasad, R
Nutrition research (New York, N.Y.). 2021;:109-128
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Abstract
Novel coronavirus disease 2019 (COVID-19) has spread across the globe; and surprisingly, no potentially protective or therapeutic antiviral molecules are available to treat severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. However, zinc (Zn) and copper (Cu) have been shown to exert protective effects due to their antioxidant, anti-inflammatory, and antiviral properties. Therefore, it is hypothesized that supplementation with Zn and Cu alone or as an adjuvant may be beneficial with promising efficacy and a favorable safety profile to mitigate symptoms, as well as halt progression of the severe form of SARS-CoV-2 infection. The objective of this review is to discuss the proposed underlying molecular mechanisms and their implications for combating SARS-CoV-2 infection in response to Zn and Cu administration. Several clinical trials have also included the use of Zn as an adjuvant therapy with dietary regimens/antiviral drugs against COVID-19 infection. Overall, this review summarizes that nutritional intervention with Zn and Cu may offer an alternative treatment strategy by eliciting their virucidal effects through several fundamental molecular cascades, such as, modulation of immune responses, redox signaling, autophagy, and obstruction of viral entry and genome replication during SARS-CoV-2 infection.
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Dietary Phytochemicals in Zinc Homeostasis: A Strategy for Prostate Cancer Management.
Singh, CK, Chhabra, G, Patel, A, Chang, H, Ahmad, N
Nutrients. 2021;(6)
Abstract
Studies have suggested an important role of the trace element zinc (Zn) in prostate biology and functions. Zn has been shown to exist in very high concentrations in the healthy prostate and is important for several prostatic functions. In prostate cancer (PCa), Zn levels are significantly decreased and inversely correlated with disease progression. Ideally, restoration of adequate Zn levels in premalignant/malignant prostate cells could abort prostate malignancy. However, studies have shown that Zn supplementation is not an efficient way to significantly increase Zn concentrations in PCa. Based on a limited number of investigations, the reason for the lower levels of Zn in PCa is believed to be the dysregulation of Zn transporters (especially ZIP and ZnT family of proteins), metallothioneins (for storing and releasing Zn), and their regulators (e.g., Zn finger transcription factor RREB1). Interestingly, the level of Zn in cells has been shown to be modulated by naturally occurring dietary phytochemicals. In this review, we discussed the effect of selected phytochemicals (quercetin, resveratrol, epigallocatechin-3-gallate and curcumin) on Zn functioning and proposes that Zn in combination with specific dietary phytochemicals may lead to enhanced Zn bioaccumulation in the prostate, and therefore, may inhibit PCa.
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Can Zn Be a Critical Element in COVID-19 Treatment?
Rahman, MT, Idid, SZ
Biological trace element research. 2021;(2):550-558
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Abstract
The current COVID-19 pandemic caused by SARS-CoV-2 has prompted investigators worldwide to search for an effective anti-viral treatment. A number of anti-viral drugs such as ribavirin, remdesivir, lopinavir/ritonavir, antibiotics such as azithromycin and doxycycline, and anti-parasite such as ivermectin have been recommended for COVID-19 treatment. In addition, sufficient pre-clinical rationale and evidence have been presented to use chloroquine for the treatment of COVID-19. Furthermore, Zn has the ability to enhance innate and adaptive immunity in the course of a viral infection. Besides, Zn supplement can favour COVID-19 treatment using those suggested and/or recommended drugs. Again, the effectiveness of Zn can be enhanced by using chloroquine as an ionophore while Zn inside the infected cell can stop SARS-CoV-2 replication. Given those benefits, this perspective paper describes how and why Zn could be given due consideration as a complement to the prescribed treatment of COVID-19.
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Zinc Biofortification in Food Crops Could Alleviate the Zinc Malnutrition in Human Health.
Praharaj, S, Skalicky, M, Maitra, S, Bhadra, P, Shankar, T, Brestic, M, Hejnak, V, Vachova, P, Hossain, A
Molecules (Basel, Switzerland). 2021;(12)
Abstract
Micronutrient malnutrition is a global health issue and needs immediate attention. Over two billion people across the globe suffer from micronutrient malnutrition. The widespread zinc (Zn) deficiency in soils, poor zinc intake by humans in their diet, low bioavailability, and health consequences has led the research community to think of an economic as well as sustainable strategy for the alleviation of zinc deficiency. Strategies like fortification and diet supplements, though effective, are not economical and most people in low-income countries cannot afford them, and they are the most vulnerable to Zn deficiency. In this regard, the biofortification of staple food crops with Zn has been considered a useful strategy. An agronomic biofortification approach that uses crop fertilization with Zn-based fertilizers at the appropriate time to ensure grain Zn enrichment has been found to be cost-effective, easy to practice, and efficient. Genetic biofortification, though time-consuming, is also highly effective. Moreover, a Zn-rich genotype once developed can also be used for many years without any recurring cost. Hence, both agronomic and genetic biofortification can be a very useful tool in alleviating Zn deficiency.
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Galvanization of Protein-Protein Interactions in a Dynamic Zinc Interactome.
Kocyła, A, Tran, JB, Krężel, A
Trends in biochemical sciences. 2021;(1):64-79
Abstract
The presence of Zn2+ at protein-protein interfaces modulates complex function, stability, and introduces structural flexibility/complexity, chemical selectivity, and reversibility driven in a Zn2+-dependent manner. Recent studies have demonstrated that dynamically changing Zn2+ affects numerous cellular processes, including protein-protein communication and protein complex assembly. How Zn2+-involved protein-protein interactions (ZPPIs) are formed and dissociate and how their stability and reactivity are driven in a zinc interactome remain poorly understood, mostly due to experimental obstacles. Here, we review recent research advances on the role of Zn2+ in the formation of interprotein sites, their architecture, function, and stability. Moreover, we underline the importance of zinc networks in intersystemic communication and highlight bioinformatic and experimental challenges required for the identification and investigation of ZPPIs.
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Vitamin D, zinc and glutamine: Synergistic action with OncoTherad immunomodulator in interferon signaling and COVID‑19 (Review).
Name, JJ, Vasconcelos, AR, Souza, ACR, Fávaro, WJ
International journal of molecular medicine. 2021;(3)
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Abstract
Coronavirus disease 2019 (COVID‑19), caused by severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2), was identified in December, 2019 in Wuhan, China. Since then, it has continued to spread rapidly in numerous countries, while the search for effective therapeutic options persists. Coronaviruses, including SARS‑CoV‑2, are known to suppress and evade the antiviral responses of the host organism mediated by interferon (IFN), a family of cytokines that plays an important role in antiviral defenses associated with innate immunity, and has been used therapeutically for chronic viral diseases and cancer. On the other hand, OncoTherad, a safe and effective immunotherapeutic agent in the treatment of non‑muscle invasive bladder cancer (NMIBC), increases IFN signaling and has been shown to be a promising therapeutic approach for COVID‑19 in a case report that described the rapid recovery of a 78‑year‑old patient with NMIBC with comorbidities. The present review discusses the possible synergistic action of OncoTherad with vitamin D, zinc and glutamine, nutrients that have been shown to facilitate immune responses mediated by IFN signaling, as well as the potential of this combination as a therapeutic option for COVID‑19.
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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.