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Antibacterial Titanium Implants Biofunctionalized by Plasma Electrolytic Oxidation with Silver, Zinc, and Copper: A Systematic Review.
van Hengel, IAJ, Tierolf, MWAM, Fratila-Apachitei, LE, Apachitei, I, Zadpoor, AA
International journal of molecular sciences. 2021;(7)
Abstract
Patients receiving orthopedic implants are at risk of implant-associated infections (IAI). A growing number of antibiotic-resistant bacteria threaten to hamper the treatment of IAI. The focus has, therefore, shifted towards the development of implants with intrinsic antibacterial activity to prevent the occurrence of infection. The use of Ag, Cu, and Zn has gained momentum as these elements display strong antibacterial behavior and target a wide spectrum of bacteria. In order to incorporate these elements into the surface of titanium-based bone implants, plasma electrolytic oxidation (PEO) has been widely investigated as a single-step process that can biofunctionalize these (highly porous) implant surfaces. Here, we present a systematic review of the studies published between 2009 until 2020 on the biomaterial properties, antibacterial behavior, and biocompatibility of titanium implants biofunctionalized by PEO using Ag, Cu, and Zn. We observed that 100% of surfaces bearing Ag (Ag-surfaces), 93% of surfaces bearing Cu (Cu-surfaces), 73% of surfaces bearing Zn (Zn-surfaces), and 100% of surfaces combining Ag, Cu, and Zn resulted in a significant (i.e., >50%) reduction of bacterial load, while 13% of Ag-surfaces, 10% of Cu-surfaces, and none of Zn or combined Ag, Cu, and Zn surfaces reported cytotoxicity against osteoblasts, stem cells, and immune cells. A majority of the studies investigated the antibacterial activity against S. aureus. Important areas for future research include the biofunctionalization of additively manufactured porous implants and surfaces combining Ag, Cu, and Zn. Furthermore, the antibacterial activity of such implants should be determined in assays focused on prevention, rather than the treatment of IAIs. These implants should be tested using appropriate in vivo bone infection models capable of assessing whether titanium implants biofunctionalized by PEO with Ag, Cu, and Zn can contribute to protect patients against IAI.
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Does Evidence Exist to Blunt Inflammatory Response by Nutraceutical Supplementation during COVID-19 Pandemic? An Overview of Systematic Reviews of Vitamin D, Vitamin C, Melatonin, and Zinc.
Corrao, S, Mallaci Bocchio, R, Lo Monaco, M, Natoli, G, Cavezzi, A, Troiani, E, Argano, C
Nutrients. 2021;(4)
Abstract
More than one year has passed since the first cases of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome (SARS)-CoV-2 coronavirus were reported in Wuhan (China), rapidly evolving into a global pandemic. This infectious disease has become a major public health challenge in the world. Unfortunately, to date, no specific antivirals have been proven to be effective against COVID-19, and although a few vaccines are available, the mortality rate is not decreasing but is still increasing. One therapeutic strategy has been focused on infection prevention and control measures. In this regard, the use of nutraceutical supports may play a role against some aspect of the infection, particularly the inflammatory state and the immune system function of patients, thus representing a strategy to control the worst outcomes of this pandemic. For this reason, we performed an overview including meta-analyses and systematic reviews to assess the association among melatonin, vitamin C, vitamin D, zinc supplementation and inflammatory markers using three databases, namely, MEDLINE, PubMed Central and the Cochrane Library of Systematic Reviews. According to the evidence available, an intake of 50,000 IU/month of vitamin D showed efficacy in CRP. An amount of 1 to 2 g per day of vitamin C demonstrated efficacy both in CRP and endothelial function, and a dosage of melatonin ranging from 5 to 25 mg /day showed good evidence of efficacy in CRP, TNF and IL6. A dose of 50 mg/day of elemental zinc supplementation showed positive results in CRP. Based on the data reported in this review, the public health system could consider whether it is possible to supplement the current limited preventive measures through targeted nutraceutical large-scale administration.
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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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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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Prediction of survival odds in COVID-19 by zinc, age and selenoprotein P as composite biomarker.
Heller, RA, Sun, Q, Hackler, J, Seelig, J, Seibert, L, Cherkezov, A, Minich, WB, Seemann, P, Diegmann, J, Pilz, M, et al
Redox biology. 2021;:101764
Abstract
SARS-CoV-2 infections cause the current coronavirus disease (COVID-19) pandemic and challenge the immune system with ongoing inflammation. Several redox-relevant micronutrients are known to contribute to an adequate immune response, including the essential trace elements zinc (Zn) and selenium (Se). In this study, we tested the hypothesis that COVID-19 patients are characterised by Zn deficiency and that Zn status provides prognostic information. Serum Zn was determined in serum samples (n = 171) collected consecutively from patients surviving COVID-19 (n = 29) or non-survivors (n = 6). Data from the European Prospective Investigation into Cancer and Nutrition (EPIC) study were used for comparison. Zn concentrations in patient samples were low as compared to healthy subjects (mean ± SD; 717.4 ± 246.2 vs 975.7 ± 294.0 μg/L, P < 0.0001). The majority of serum samples collected at different time points from the non-survivors (25/34, i.e., 73.5%) and almost half of the samples collected from the survivors (56/137, i.e., 40.9%) were below the threshold for Zn deficiency, i.e., below 638.7 μg/L (the 2.5th percentile in the EPIC cohort). In view that the Se status biomarker and Se transporter selenoprotein P (SELENOP) is also particularly low in COVID-19, we tested the prevalence of a combined deficit, i.e., serum Zn below 638.7 μg/L and serum SELENOP below 2.56 mg/L. This combined deficit was observed in 0.15% of samples in the EPIC cohort of healthy subjects, in 19.7% of the samples collected from the surviving COVID-19 patients and in 50.0% of samples from the non-survivors. Accordingly, the composite biomarker (SELENOP and Zn with age) proved as a reliable indicator of survival in COVID-19 by receiver operating characteristic (ROC) curve analysis, yielding an area under the curve (AUC) of 94.42%. We conclude that Zn and SELENOP status within the reference ranges indicate high survival odds in COVID-19, and assume that correcting a diagnostically proven deficit in Se and/or Zn by a personalised supplementation may support convalescence.
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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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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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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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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.