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Zinc supplementation is associated with a reduction in serum markers of inflammation and oxidative stress in adults: A systematic review and meta-analysis of randomized controlled trials.
Hosseini, R, Ferns, GA, Sahebkar, A, Mirshekar, MA, Jalali, M
Cytokine. 2021;:155396
Abstract
BACKGROUND Zinc (Zn) is a trace metal that is considered to have an impact on chronic inflammation. However, findings of clinical trials have been inconsistent. The present systematic review and meta-analysis aimed to provide a more robust examination of the evidence on the effectiveness of Zn supplements on markers of inflammation and oxidative stress. METHODS A systematic search in PubMed, Scopus, Web of Science and Cochrane Library was undertaken to identify relevant randomized controlled trials (RCTs) assessing the impact of Zn on inflammation and oxidative stress until 17 August 2020. We applied a random-effects method to obtain effect sizes (ES) and 95% confidence intervals (CIs). Meta-regression was used to detect the potential source of between-study heterogeneity. RESULTS Twenty-one eligible RCTs comprising 1321 participants were included in the meta-analysis. In comparison with the control groups, serum C-reactive protein (CRP) (ES = -0.92 mg/L, 95% CI = [-1.36, -0.48], P < 0.001, I2 = 90.2%), tumor necrosis factor-alpha (TNF-α) (ES = -0.49 pg/mL, 95% CI = [-084, -0.14], P = 0.006, I2 = 34.6%) and malondialdehyde (MDA) (ES = -0.42, 95% CI = [-083, -0.01], P = 0.04, I2 = 76.1%) were significantly reduced in the groups receiving Zn. Serum interleukin 6 (ES = -1.02 pg/mL, 95% CI = [-2.06, 0.02], P = 0.05, I2 = 92.3%) was marginally reduced following Zn supplementation. Moreover, treatment duration was found as the source of inter-study heterogeneity. CONCLUSION This meta-analysis suggests that Zn supplements reduce serum concentrations of markers of inflammation and oxidation: CRP, TNF-α and MDA.
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2.
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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The Minimal Effect of Zinc on the Survival of Hospitalized Patients With COVID-19: An Observational Study.
Yao, JS, Paguio, JA, Dee, EC, Tan, HC, Moulick, A, Milazzo, C, Jurado, J, Della Penna, N, Celi, LA
Chest. 2021;(1):108-111
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Profiling inflammatory cytokines following zinc supplementation: a systematic review and meta-analysis of controlled trials.
Faghfouri, AH, Baradaran, B, Khabbazi, A, Khaje Bishak, Y, Zarezadeh, M, Tavakoli-Rouzbehani, OM, Faghfuri, E, Payahoo, L, Alipour, M, Alipour, B
The British journal of nutrition. 2021;(10):1441-1450
Abstract
Chronic inflammation has been considered as the main cause of chronic diseases. Zn has anti-inflammatory effects by decreasing the expression of inflammatory markers. The present systematic review and meta-analysis study aims to evaluate the impact of Zn supplementation on inflammation. PubMed (Medline), Scopus, Web of Science, and Embase databases were searched up to 10 December 2020. Controlled trials which have investigated the effects of Zn supplementation on serum/plasma levels of inflammatory cytokines in subjects aged >15 years were included. A pooled meta-analysis was performed using a random effect model. Sensitivity analysis was performed to determine the robustness of the observed effect sizes. A total of twelve studies was included in meta-analysis. Zn could decrease IL-6 levels (standardised mean difference (SMD) = -0·76 pg/ml; 95 % CI -1·28, -0·24; P = 0·004). There was no significant change in TNF-α (SMD = 0·42 pg/ml; 95 % CI -0·31, 1·16; P = 0·257) and IL-2 levels (SMD = 1·64 pg/ml; 95 % CI -1·31, 4·59; P = 0·277) following Zn supplementation. However, Zn could increase IL-2 significantly after the deletion of one arm in sensitivity analysis (SMD = 2·96 pg/ml; 95 % CI 2·03, 3·88; P < 0·05). Conclusively, Zn supplementation can decrease the IL-6 level. Zn increased IL-2 level after the sensitivity analysis. Zn supplementation has not ameliorative effects on TNF-α.
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5.
Identification of unique subtype-specific interaction features in Class II zinc-dependent HDAC subtype binding pockets: A computational study.
Ukey, S, Choudhury, C, Sharma, P
Journal of biosciences. 2021
Abstract
Zinc-dependent HDAC subtypes (ZnHDACs) exhibit differential expression in various cancer types and significantly contribute to oncogenic cell transformation, and hence are interesting anticancer drug targets. The approved pan HDAC inhibitors (PHIs) lack subtype specificity and inhibit all ZnHDACs, causing severe sideeffects. Considering the distinct tissue distribution and roles of individual ZnHDACs in specific cancer types, it is crucial to rationally design subtype-specific inhibitors (SSIs) for enhanced efficacy and reduced side-effects. There are numerous approaches already conducted for designing SSIs, especially Class I ZnHDACs, whereas Class II and III ZnHDACs are relatively unexplored and equally important in disease pathogenesis. This study attempts to decipher the specificity rendering interaction features of six different ZnHDACs by robust analyses of reported experimental data employing sophisticated computational methods like homology modelling, docking, pharmacophore analysis, and molecular dynamic (MD) simulations. Experimentally validated SSIs (activity<1000 nM) of different ZnHDACs and 8 approved PHIs were docked to 40 MD generated conformations of each ZnHDACs followed by MM-GBSA binding energy estimations. Sequences, structures, physicochemical properties, and interaction patterns of the binding sites obtained from docking were exhaustively compared to identify unique subtype-specific interaction features for each Class II ZnHDACs. To further validate the stabilities of these features, 20 ns MD simulations were performed on 12 complexes (each Class II ZnHDACs bound to one SSI and one PHI) in explicit water models. Distinct pharmacophoric patterns were observed in the binding pockets of each subtype despite high sequence similarities. Presence of amides, ketone, hydroxyl, carboxyl groups, and moieties occupying additional sub-pockets and interacting with Zn 2+, etc., in the SSIs affect the orientations of the binding site residues (BSRs) owing to subtype-specific protein- ligand interactions. Stable and unique residue interactions specific for a HDAC subtype are, e.g. E329 for HDAC4, S904 for HDAC5, W496 S563 I569 for HDAC6, M793 for HDAC9, and E302 for HDAC10. Such unique interaction features and pharmacophoric patterns can be utilized for subtype-specific ZnHDAC inhibitor design.
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6.
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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Aristocratic human papillomavirus drove cervical cancer: a study of the therapeutic potential of the combination of interferon with zinc.
Gao, YH, Yu, L, Liu, ZS, Li, YF
Molecular and cellular biochemistry. 2021;(2):757-765
Abstract
Human papillomavirus (HPV) infection is related to cancer growth of vaginal, cervical, vulva, penile, anogenital, and non-genital oropharyngeal sites. HPV, as a sexually transmitted virus, infects all sexes similarly but with more significant pathological risks in women. This accounts for high mortality due to late detection and poor prognosis. The initial development and eventual progress of this cancer type depend entirely on three main oncogenes E5, E6 and E7, constitutively expressed to lead to carcinogenesis. Despite an opportunity for pharmacological therapy, there is still a shortage of medical treatment that may remove HPV from infected lesions. This study offers a concise summary of the nature of the issue and the current status of work on potential lead molecules and therapeutic approaches that show the capacity of HPV therapies to counteract the roles of deregulation of E5, E6, and E7.
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8.
Zn2+ influx activates ERK and Akt signaling pathways.
Anson, KJ, Corbet, GA, Palmer, AE
Proceedings of the National Academy of Sciences of the United States of America. 2021;(11)
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Abstract
Zinc (Zn2+) is an essential metal in biology, and its bioavailability is highly regulated. Many cell types exhibit fluctuations in Zn2+ that appear to play an important role in cellular function. However, the detailed molecular mechanisms by which Zn2+ dynamics influence cell physiology remain enigmatic. Here, we use a combination of fluorescent biosensors and cell perturbations to define how changes in intracellular Zn2+ impact kinase signaling pathways. By simultaneously monitoring Zn2+ dynamics and kinase activity in individual cells, we quantify changes in labile Zn2+ and directly correlate changes in Zn2+ with ERK and Akt activity. Under our experimental conditions, Zn2+ fluctuations are not toxic and do not activate stress-dependent kinase signaling. We demonstrate that while Zn2+ can nonspecifically inhibit phosphatases leading to sustained kinase activation, ERK and Akt are predominantly activated via upstream signaling and through a common node via Ras. We provide a framework for quantification of Zn2+ fluctuations and correlate these fluctuations with signaling events in single cells to shed light on the role that Zn2+ dynamics play in healthy cell signaling.
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Survival of Laryngeal Cancer Patients Depending on Zinc Serum Level and Oxidative Stress Genotypes.
Lubiński, J, Jaworowska, E, Derkacz, R, Marciniak, W, Białkowska, K, Baszuk, P, Scott, RJ, Lubiński, JA
Biomolecules. 2021;(6)
Abstract
Stress contributes to various aspects of malignancy and could influence survival in laryngeal cancer patients. Among antioxidant mechanisms, zinc and the antioxidant enzymes superoxide dismutase 2, catalase and glutathione peroxidase 1 play a major role. The aim of this study was a prospective evaluation of the survival of patients with laryngeal cancer in relation to serum levels of zinc in combination with functional genotype differences of three key antioxidant enzymes. The study group consisted of 300 patients treated surgically for laryngeal cancer. Serum zinc levels and common polymorphisms in SOD2, CAT and GPX1 were analyzed. The risk of death in patients with the lowest zinc levels was increased in comparison with patients with the highest levels. Polymorphisms of antioxidant genes by themselves were not correlated with survival, however, serum zinc level impact on survival was stronger for SOD2 TC/TT and CAT CC variants. GPX1 polymorphisms did not correlate with zinc levels regarding survival. In conclusion, serum zinc concentration appears to be an important prognostic factor for survival of patients diagnosed with laryngeal cancer. When higher zinc levels were correlated with polymorphisms in SOD2 and CAT a further increase in survival was observed.
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Incidence of hyperaccumulation and tissue-level distribution of manganese, cobalt, and zinc in the genus Gossia (Myrtaceae).
Abubakari, F, Nkrumah, PN, Fernando, DR, Brown, GK, Erskine, PD, Echevarria, G, van der Ent, A
Metallomics : integrated biometal science. 2021;(4)
Abstract
The rare phenomenon of plant manganese (Mn) hyperaccumulation within the Australian flora has previously been detected in the field, which suggested that the tree genus Gossia (Myrtaceae) might contain new Mn hyperaccumulators. We conducted the first growth experiment on Gossia using a multi-factorial dosing trial to assess Mn, cobalt (Co), and zinc (Zn) (hyper)accumulation patterns in selected Gossia species (G. fragrantissima and G. punctata) after a systematic assessment of elemental profiles on all holdings of the genus Gossia at the Queensland Herbarium using handheld X-ray fluorescence spectroscopy. We then conducted detailed in situ analyses of the elemental distribution of Mn, Co, Zn and other elements at the macro (organ) and micro (cellular) levels with laboratory- and synchrotron-based X-ray fluorescence microscopy (XFM). Gossia pubiflora and Gossia hillii were newly discovered to be Mn hyperaccumulator plants. In the dosing trial, G. fragrantissima accumulated 17 400 µg g-1 Mn, 545 µg g-1 Co, and 13 000 µg g-1 Zn, without signs of toxicity. The laboratory-based XFM revealed distinct patterns of accumulation of Co, Mn, and Zn in G. fragrantissima, while the synchrotron XFM showed their localization in foliar epidermal cells, and in the cortex and phloem cells of roots. This study combined novel analytical approaches with controlled experimentation to examine metal hyperaccumulation in slow-growing tropical woody species, thereby enabling insight into the phenomenon not possible through field studies.