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Johari B, Tavangar-Roosta S, Gharbavi M, Sharafi A, Kaboli S, Rezaeejam H. Suppress the cell growth of cancer stem-like cells (NTERA-2) using Sox2-Oct4 decoy oligodeoxynucleotide-encapsulated niosomes-zinc hybrid nanocarriers under X-irradiation. Heliyon 2024; 10:e34096. [PMID: 39071677 PMCID: PMC11277410 DOI: 10.1016/j.heliyon.2024.e34096] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2023] [Revised: 07/02/2024] [Accepted: 07/03/2024] [Indexed: 07/30/2024] Open
Abstract
Sox2 and Oct4 dysregulations could significantly increase in the cancer stem cell (CSC) population in some cancer cells and resistance to common treatments. In this study, the synergistic effects of Sox2-Oct4 decoy oligodeoxynucleotides-encapsulated Niosomes-zinc hybrid nanocarriers along with X-irradiation conditions as a combinational therapy tool were investigated in the treatment of cancer-like stem cells (NTERA-2). The NTERA-2 cell line known as a cancer-like stem cell line was used in this investigation. Sox2-Oct4 decoy oligodeoxynucleotides were designed based on the sequence of the Sox2 promoter and synthesized. Physicochemical characteristics of ODNs-encapsulated niosomes-zinc hybrid nanocarriers (NISM@BSA-DEC-Zn) investigated with FT-IR, DLS, FESEM, and ODNs release kinetic estimation assays. Further investigations such as hemolysis, uptake, cell viability, apoptosis, cell cycle, and scratch repair tests were performed. All the above assays were completed with and without X-ray exposure conditions (fractionated 2Gy). Physicochemical characteristics results showed that the Niosomes-Zn nanocarriers were successfully synthesized. NISM@BSA-DEC-Zn was efficiently taken up by NTERA-2 cells and significantly inhibited cell growth, increased apoptosis, and reduced cell migration in both conditions (with and without X-ray exposure). Furthermore, NISM@BSA-DEC-Zn treatment resulted in G1 and G2/M cell cycle arrest without and with X-irradiation, respectively. The prepared nanocarrier system can be a promising tool for drug delivery in cancer treatment. Decoy ODN strategy along with zinc nanoparticles could increase the sensitivity of cancer cells toward irradiation, which has the potential for combinational cancer therapies.
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Affiliation(s)
- Behrooz Johari
- Zanjan Pharmaceutical Biotechnology Research Center, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Shabnam Tavangar-Roosta
- Department of Medical Biotechnology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Mahmoud Gharbavi
- Nanotechnology Research Center, Medical Basic Scinces Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
- Pain Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Ali Sharafi
- Zanjan Pharmaceutical Biotechnology Research Center, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Saeed Kaboli
- Department of Medical Biotechnology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Hamed Rezaeejam
- Department of Radiology Technology, School of Allied Medical Sciences, Zanjan University of Medical Sciences, Zanjan, Iran
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Singh A, Choudhury SD, Singh P, Singh VV, Singh SN, Sharma A. Ionic reverberation modulates the cellular fate of CD8 +tissue resident memory T cells (TRMs) in patients with renal cell carcinoma: A novel mechanism. Clin Immunol 2024; 264:110256. [PMID: 38762062 DOI: 10.1016/j.clim.2024.110256] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2024] [Revised: 05/02/2024] [Accepted: 05/14/2024] [Indexed: 05/20/2024]
Abstract
In metastatic renal cell carcinoma (mRCC), existing treatments including checkpoint inhibitors are failed to cure and/or prevent recurrence of the disease. Therefore, in-depth understanding of tumor tissue resident memory T cells (TRMs) dysfunction are necessitated to enrich efficacy of immunotherapies and increasing disease free survival in treated patients. In patients, we observed dysregulation of K+, Ca2+, Na2+ and Zn2+ ion channels leads to excess infiltration of their respective ions in tumor TRMs, thus ionic gradients are disturbed and cells became hyperpolarized. Moreover, overloaded intramitochondrial calcium caused mitochondrial depolarization and trigger apoptosis of tumor TRMs. Decreased prevalence of activated tumor TRMs reflected our observations. Furthermore, disruptions in ionic concentrations impaired the functional activities and/or suppressed anti-tumor action of circulating and tumor TRMs in RCC. Collectively, these findings revealed novel mechanism behind dysfunctionality of tumor TRMs. Implicating enrichment of activated TRMs within tumor would be beneficial for better management of RCC patients.
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Affiliation(s)
- Ashu Singh
- Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India
| | - Saumitra Dey Choudhury
- Central core Research facility, All India Institute of Medical Sciences, New Delhi, India
| | - Prabhjot Singh
- Department of Urology, All India Institute of Medical Sciences, New Delhi, India
| | | | - Som Nath Singh
- Defence Institute of Physiology and Allied Sciences, New Delhi, India
| | - Alpana Sharma
- Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India.
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Mairinger E, Wessolly M, Buderath P, Borchert S, Henrich L, Mach P, Steinborn J, Kimming R, Jasani B, Schmid KW, Bankfalvi A, Mairinger FD. Tumor cell cytoplasmic metallothionein expression associates with differential tumor immunogenicity and prognostic outcome in high-grade serous ovarian carcinoma. Front Oncol 2023; 13:1252700. [PMID: 38023247 PMCID: PMC10663300 DOI: 10.3389/fonc.2023.1252700] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2023] [Accepted: 10/20/2023] [Indexed: 12/01/2023] Open
Abstract
Background The underlying mechanism of high T-cell presence as a favorable prognostic factor in high-grade serous ovarian carcinoma (HGSOC) is not yet understood. In addition to immune cells, various cofactors are essential for immune processes. One of those are metallothioneins (MTs), metal-binding proteins comprising various isoforms. MTs play a role in tumor development and drug resistance. Moreover, MTs influence inflammatory processes by regulating zinc homeostasis. In particular, T-cell function and polarization are particularly susceptible to changes in zinc status. The aim of the present study was to investigate a possible role of MT-mediated immune response and its association with prognostic outcome in ovarian cancer. Methods A retrospective study was conducted on a clinically well-characterized cohort of 24 patients with HGSOC treated at the University Hospital of Essen. Gene expression patterns for anti-cancer immunogenicity-related targets were performed using the NanoString nCounter platform for digital gene expression analysis with the appurtenant PanCancer Immune Profiling panel, consisting of 770 targets and 30 reference genes. Tumor-associated immunohistochemical MT protein expression was evaluated using a semi-quantitative four-tier Immunohistochemistry (IHC) scoring. Results MT immunoexpression was detected in 43% (10/23) of all HGSOC samples. MT immunoexpression levels showed a significant association to survival, leading to prolonged progression-free and overall survival in positively stained tumors. Furthermore, T-cell receptor signaling gene signature showed a strong activation in MT-positive tumors. Activated downstream signaling cascades resulting in elevated interferon-gamma expression with a shift in the balance between T helper cells (TH1 and TH2) could be observed in the MT-positive subgroup. In addition, a higher expression pattern of perforin and several granzymes could be detected, overall suggestive of acute, targeted anti-cancer immune response in MT-positive samples. Conclusion This is the first study combining broad, digital mRNA screening of anti-tumor immune response-associated genes and their relation to MT-I/II in ovarian cancer. MT overexpression is associated with molecular characteristics of an anti-cancer immune response and is a strong prognostic marker in ovarian HGSOC. The observed immune cell activation associated with tumor MT expression comprises but is not limited to T cells and natural killer cells.
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Affiliation(s)
- Elena Mairinger
- Institute of Pathology, University Hospital Essen, Essen, Germany
| | - Michael Wessolly
- Department of Gynecology and Obstetrics, University Hospital Essen, Essen, Germany
| | - Paul Buderath
- Department of Gynecology and Obstetrics, University Hospital Essen, Essen, Germany
| | - Sabrina Borchert
- Institute of Pathology, University Hospital Essen, Essen, Germany
| | - Larissa Henrich
- Institute of Pathology, University Hospital Essen, Essen, Germany
| | - Pawel Mach
- Department of Gynecology and Obstetrics, University Hospital Essen, Essen, Germany
| | - Julia Steinborn
- Institute of Pathology, University Hospital Essen, Essen, Germany
| | - Rainer Kimming
- Department of Gynecology and Obstetrics, University Hospital Essen, Essen, Germany
| | - Bharat Jasani
- Department of Pathology, Targos - A Discovery Life Sciences Company, Kassel, Germany
| | | | - Agnes Bankfalvi
- Institute of Pathology, University Hospital Essen, Essen, Germany
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Sampath V, Cho S, Lee BR, Kim NH, Kim IH. Enhancement of protective vaccine-induced antibody titer to swine diseases and growth performance by Amino-Zn, yucca extract, and β-mannanase feed additive in wean-finishing pigs. Front Vet Sci 2023; 10:1095877. [PMID: 37662989 PMCID: PMC10470888 DOI: 10.3389/fvets.2023.1095877] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2022] [Accepted: 07/26/2023] [Indexed: 09/05/2023] Open
Abstract
The primary purpose of this research is to determine the effect of Amino-Zn (AZn), Yucca schidigera extract (YE), and β-mannanase enzyme supplementation on growth performance, nutrient digestibility, fecal gas emission, and immune response in pigs. A total of 180 crossbred pigs (6.57 ± 1 kg) were randomly assigned to one of three dietary treatments: CON-corn soybean meal (basal diet); TRT1-CON +1,000 ppm AZn + 0.07% yucca extract (YE) + 0.05% β-mannanase; and TRT2-CON +2,000 ppm AZn + 0.07% YE+ 0.05% β-mannanase for 22 weeks. Each treatment had 12 replicates with 5 pigs per pen. Pigs fed a diet supplemented with AZn, YE, and β-mannanase linearly increased (p < 0.05) BW and average daily gain at weeks 6, 12, 17, and 18. In contrast, the gain-to-feed ratio showed a linear increase (p < 0.05) from weeks 6 to 17 and the overall trial period. Moreover, the inclusion of experimental diets linearly decreased (p > 0.05) noxious gas emissions such as ammonia, hydrogen sulfide, acetic acid, carbon dioxide, and methyl mercaptans. The dietary inclusion of AZn, YE, and β-mannanase significantly increased the serological immune responses to Mycoplasma hyopneumoniae (MH) and foot-and-mouth disease virus (FMDV-O type) at the end of week 6 and porcine circovirus-2 (PCV-2) at week 19. Based on this result, we infer that the combination of AZn, YE, and β-mannanase supplement would serve as a novel in-feed additive to enhance growth performance and act as a boosting agent and immune stimulatory to increase the efficacy of swine vaccinations.
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Affiliation(s)
- Vetriselvi Sampath
- Department of Animal Resources, Dankook University, Cheonan, Republic of Korea
| | - Sungbo Cho
- Department of Animal Resources, Dankook University, Cheonan, Republic of Korea
| | | | - Nam-Hun Kim
- ZinexBio Corporation, Asan, Republic of Korea
| | - In Ho Kim
- Department of Animal Resources, Dankook University, Cheonan, Republic of Korea
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Zhu L, An P, Zhao W, Xia Y, Qi J, Luo J, Luo Y. Low Zinc Alleviates the Progression of Thoracic Aortic Dissection by Inhibiting Inflammation. Nutrients 2023; 15:1640. [PMID: 37049478 PMCID: PMC10096567 DOI: 10.3390/nu15071640] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2023] [Revised: 03/24/2023] [Accepted: 03/24/2023] [Indexed: 03/30/2023] Open
Abstract
Vascular inflammation triggers the development of thoracic aortic dissection (TAD). Zinc deficiency could dampen tissue inflammation. However, the role of zinc as a nutritional intervention in the progression of TAD remains elusive. In this study, we employed a classical β-aminopropionitrile monofumarate (BAPN)-induced TAD model in mice treated with low zinc and observed that the TAD progression was greatly ameliorated under low zinc conditions. Our results showed that low zinc could significantly improve aortic dissection and rupture (BAPN + low zinc vs. BAPN, 36% vs. 100%) and reduce mortality (BAPN + low zinc vs. BAPN, 22% vs. 57%). Mechanically, low zinc attenuated the infiltration of macrophages and inhibited the expression of inflammatory cytokines, suppressed the phenotype switch of vascular smooth muscle cells from contractile to synthetic types, and eventually alleviated the development of TAD. In conclusion, this study suggested that low zinc may serve as a potential nutritional intervention approach for TAD prevention.
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Affiliation(s)
- Lin Zhu
- Department of Nutrition and Health, China Agricultural University, Beijing 100193, China
- Food Laboratory of Zhongyuan, Luohe 462300, China
| | - Peng An
- Department of Nutrition and Health, China Agricultural University, Beijing 100193, China
| | - Wenting Zhao
- Department of Nutrition and Health, China Agricultural University, Beijing 100193, China
| | - Yi Xia
- Department of Nutrition and Health, China Agricultural University, Beijing 100193, China
| | - Jingyi Qi
- Department of Nutrition and Health, China Agricultural University, Beijing 100193, China
- Food Laboratory of Zhongyuan, Luohe 462300, China
| | - Junjie Luo
- Department of Nutrition and Health, China Agricultural University, Beijing 100193, China
- Food Laboratory of Zhongyuan, Luohe 462300, China
| | - Yongting Luo
- Department of Nutrition and Health, China Agricultural University, Beijing 100193, China
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Impact of Maternal and Offspring Dietary Zn Supplementation on Growth Performance and Antioxidant and Immune Function of Offspring Broilers. Antioxidants (Basel) 2022; 11:antiox11122456. [PMID: 36552664 PMCID: PMC9774261 DOI: 10.3390/antiox11122456] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2022] [Revised: 12/04/2022] [Accepted: 12/07/2022] [Indexed: 12/15/2022] Open
Abstract
The current study investigated the effects of the maternal Zn source in conjunction with their offspring’s dietary Zn supplementation on the growth performance, antioxidant status, Zn concentration, and immune function of the offspring. It also explored whether there is an interaction between maternal Zn and their offspring’s dietary Zn. One-day-old Lingnan Yellow-feathered broilers (n = 800) were completely randomized (n = 4) between two maternal dietary supplemental Zn sources [maternal Zn−Gly (oZn) vs. maternal ZnSO4 (iZn)] × two offspring dietary supplemental Zn doses [Zn-unsupplemented control diet (CON), the control diet + 80 mg of Zn/kg of diet as ZnSO4]. oZn increased progeny ADG and decreased offspring mortality across all periods, especially during the late periods (p < 0.05). The offspring diet supplemented with Zn significantly improved ADG and decreased offspring mortality over the whole period compared with the CON group (p < 0.05). There were significant interactions between the maternal Zn source and offspring dietary Zn with regards to progeny mortality during the late phase and across all phases as a whole (p < 0.05). Compared with the iZn group, the oZn treatment significantly increased progeny liver and serum Zn concentrations; antioxidant capacity in the liver, muscle, and serum; and the IgM concentration in serum; while also decreasing progeny serum IL-1 and TNF-α cytokine secretions (p < 0.05). Similar results were observed when the offspring diet was supplemented with Zn compared with the CON group; moreover, adding Zn to the offspring diet alleviated progeny stress by decreasing corticosterone levels in the serum when compared to the CON group (p < 0.05). In conclusion, maternal Zn−Gly supplementation increased progeny performance and decreased progeny mortality and stress by increasing progeny Zn concentration, antioxidant capacity, and immune function compared with the same Zn levels from ZnSO4. Simultaneously, Zn supplementation in the progeny’s diet is necessary for the growth of broilers.
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Kunutsor SK, Voutilainen A, Laukkanen JA. Serum copper-to-zinc ratio and risk of incident pneumonia in caucasian men: a prospective cohort study. Biometals 2022; 35:921-933. [PMID: 35781862 PMCID: PMC9546975 DOI: 10.1007/s10534-022-00414-4] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2022] [Accepted: 06/11/2022] [Indexed: 12/03/2022]
Abstract
Serum copper (Cu) and zinc (Zn), essential micronutrients that have important immunomodulatory and antimicrobial properties, are biomarkers of ageing. Serum Cu/Zn-ratio may be a more reliable marker for age-related degenerative conditions compared with serum Cu or Zn alone. We aimed to assess the association between Cu/Zn-ratio and the risk of incident pneumonia in a prospective cohort study. Serum levels of Cu and Zn were measured at baseline using atomic absorption spectrometry in 2503 men aged 42–61 years in the Kuopio Ischemic Heart Disease prospective cohort study. Hazard ratios (HRs) with confidence intervals (CIs) were calculated for incident pneumonia using Cox regression models. A total of 599 cases of pneumonia occurred during a median follow-up of 26.1 years. Serum Cu/Zn-ratio and Cu were each linearly associated with incident pneumonia. A unit increase in Cu/Zn-ratio was associated with an increased risk of pneumonia in analysis adjusted for potential confounders including C-reactive protein (HR 1.65; 95% CI 1.17–2.33). The corresponding adjusted HR (95% CI) was 2.04 (1.22–3.40) for serum Cu. The association between serum Zn and pneumonia was curvilinear. Compared to the bottom tertile of Zn, the multivariable adjusted HRs (95% CIs) for incident pneumonia were 0.68 (0.55–0.83) and 0.96 (0.79–1.16) for the middle and top tertiles of Zn, respectively. Further analysis in the same participants showed that Cu/Zn-ratio might be a stronger risk indicator for pneumonia than serum C-reactive protein. In middle-aged and older Finnish men, increased serum Cu/Zn-ratio and Cu concentrations are each linearly associated with an increased risk of incident pneumonia.
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Affiliation(s)
- Setor K Kunutsor
- National Institute for Health Research Bristol Biomedical Research Centre, University Hospitals Bristol and Weston NHS Foundation Trust and the University of Bristol, Bristol, UK.
- Musculoskeletal Research Unit, Translational Health Sciences, Bristol Medical School, University of Bristol, Learning & Research Building (Level 1), Southmead Hospital, Bristol, BS10 5NB, UK.
- Department of Medicine, Central Finland Health Care District Hospital District, Jyvaskyla, Finland.
- Diabetes Research Centre, University of Leicester, Leicester General Hospital, Gwendolen Road, Leicester, LE5 4WP, UK.
| | - Ari Voutilainen
- Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland
| | - Jari A Laukkanen
- Department of Medicine, Central Finland Health Care District Hospital District, Jyvaskyla, Finland
- Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland
- Institute of Clinical Medicine, Department of Medicine, University of Eastern Finland, Kuopio, Finland
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Baarz BR, Rink L. Rebalancing the unbalanced aged immune system - A special focus on zinc. Ageing Res Rev 2022; 74:101541. [PMID: 34915196 DOI: 10.1016/j.arr.2021.101541] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2021] [Revised: 11/18/2021] [Accepted: 12/09/2021] [Indexed: 02/08/2023]
Abstract
Nowadays, aging is understood as a dynamic and multifaceted dysregulation process that spares almost no human organ or cell. The immune system being among the most affected, it has been shown predominantly that its integrity determines the tightrope walk between the difference of escaping or suffering from age-related diseases. Next to drug-based anti-aging strategies, micronutrient intervention may represent an emerging but less radical way to slow immune aging. While a sufficient supply of a variety of micronutrients is undeniably important, adequate intake of the trace element zinc appears to tower over others in terms of reaching old age. Inconveniently, zinc deficiency prevalence among the elderly is high, which in turn contributes to increased susceptibility to infection, decreased anti-tumor immunity as well as attenuated response to vaccination. Driven by this research, this review aims to provide a comprehensive and up-to-date overview of the various rebalancing capabilities of zinc in the unbalanced immune system of the elderly. This includes an in-depth and cell type-centered discussion on the role of zinc in immunosenescence and inflammaging. We further address upcoming translational aspects e.g. how zinc deficiency promotes the flourishing of certain pathogenic taxa of the gut microbiome and how zinc supply counteracts such alterations in a manner that may contribute to longevity. In the light of the ongoing COVID-19 pandemic, we also briefly review current knowledge on the interdependency between age, zinc status, and respiratory infections. Based on two concrete examples and considering the latest findings in the field we conclude our remarks by outlining tremendous parallels between suboptimal zinc status and accelerated aging on the one hand and an optimized zinc status and successful aging on the other hand.
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Schmitt AK, Puppa MA, Wessels I, Rink L. Vitamin D3 and zinc synergistically induce regulatory T cells and suppress interferon-γ production in mixed lymphocyte culture. J Nutr Biochem 2022; 102:108942. [DOI: 10.1016/j.jnutbio.2022.108942] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2021] [Revised: 11/29/2021] [Accepted: 12/07/2021] [Indexed: 12/21/2022]
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Planeta Kepp K. Bioinorganic Chemistry of Zinc in Relation to the Immune System. Chembiochem 2021; 23:e202100554. [PMID: 34889510 DOI: 10.1002/cbic.202100554] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2021] [Revised: 12/09/2021] [Indexed: 01/18/2023]
Abstract
Zinc is well-known to have a central role in human inflammation and immunity and is itself an anti-inflammatory and antiviral agent. Despite its massively documented role in such processes, the underlying chemistry of zinc in relation to specific proteins and pathways of the immune system has not received much focus. This short review provides an overview of this topic, with emphasis on the structures of key proteins, zinc coordination chemistry, and probable mechanisms involved in zinc-based immunity, with some focus points for future chemical and biological research.
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Affiliation(s)
- Kasper Planeta Kepp
- DTU Chemistry, Technical University of Denmark, Building 206, 2800, Kongens Lyngby, Denmark
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Jiang Q, Sun J, He Y, Ma Y, Zhang B, Han Y, Wu Y. Hydroxychloride trace elements improved eggshell quality partly by modulating uterus histological structure and inflammatory cytokines expression in aged laying hens. Poult Sci 2021; 100:101453. [PMID: 34624774 PMCID: PMC8503664 DOI: 10.1016/j.psj.2021.101453] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2021] [Revised: 07/21/2021] [Accepted: 08/26/2021] [Indexed: 11/17/2022] Open
Abstract
The objectives of this study were to investigate the effectiveness of dietary zinc, copper, and manganese hydroxychloride (HC) supplementation on performance, minerals deposition, serum parameters, eggshell ultrastructure, uterus histological structure, and inflammatory cytokines in aged hens. A total of 560 Hyline Brown layers at 62 wk of age were randomly allotted into 3 groups (CON, basal diet without extra minerals supplemented; Sulphate and HC, basal diet with sulphate or hydroxychloride zinc, copper, and manganese supplementation at levels of 80, 15, and 80 mg/kg, respectively). The trial lasted for 16 wk consisting of 4 wk depletion period and 12 wk testing period. The results indicated that dietary hydroxychloride trace elements increased egg weight (P < 0.05) when compared with CON group and improved average Haugh unit and albumen height (P < 0.05) when compared with Sulphate group from 70 to 73 wk. Trace element supplementation significantly increased eggshell strength, ceruloplasmin content in serum, and modified crystallographic structure of eggshell (P < 0.05) that included effective layer height, palisade height, mammillary layer width, and mammillary internal area ratio, but the results did not differ regarding the trace mineral sources used. Furthermore, hens fed with hydroxychloride trace element showed the highest mucosal fold height (P < 0.05) and epithelial height (P = 0.053) in eggshell gland, as well as mRNA expression of TNF-α (P < 0.05) and IL-22 (P = 0.094). It is concluded that supplementation of Zn, Cu, and Mn mixture modified eggshell quality partly through enhancing histological structure and immune responses of uterus. Hydroxychloride source of Zn, Cu, and Mn excelled sulphate in its beneficial effects for birds.
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Affiliation(s)
- Qiuyu Jiang
- State Key Laboratory of Animal Nutrition, China Agricultural University, Beijing 100193, China
| | - Jingjing Sun
- State Key Laboratory of Animal Nutrition, China Agricultural University, Beijing 100193, China
| | - Yang He
- State Key Laboratory of Animal Nutrition, China Agricultural University, Beijing 100193, China
| | - Yanbo Ma
- Department of Animal Physiology, College of Animal Science and Technology, Henan University of Science and Technology, Luoyang 471023, China
| | - Bingkun Zhang
- State Key Laboratory of Animal Nutrition, China Agricultural University, Beijing 100193, China.
| | - Yanming Han
- Trouw Nutrition R&D, Amersfoort, the Netherlands
| | - Yuanyuan Wu
- Trouw Nutrition R&D, Amersfoort, the Netherlands
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Lin J, Tian H, Zhao X, Lin S, Li D, Liu Y, Xu C, Mei X. Zinc provides neuroprotection by regulating NLRP3 inflammasome through autophagy and ubiquitination in a spinal contusion injury model. CNS Neurosci Ther 2021; 27:413-425. [PMID: 33034415 PMCID: PMC7941232 DOI: 10.1111/cns.13460] [Citation(s) in RCA: 46] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2020] [Revised: 08/28/2020] [Accepted: 09/18/2020] [Indexed: 12/12/2022] Open
Abstract
AIM Spinal cord injury (SCI) is a serious disabling injury worldwide, and the excessive inflammatory response it causes plays an important role in secondary injury. Regulating the inflammatory response can be a potential therapeutic strategy for improving the prognosis of SCI. Zinc has been demonstrated to have a neuroprotective effect in experimental spinal cord injury models. In this study, we aimed to explore the neuroprotective effect of zinc through the suppression of the NLRP3 inflammasome. METHOD Allen's method was used to establish an SCI model in C57BL/6J mice. The Basso Mouse Scale (BMS), Nissl staining were employed to confirm the protective effect of zinc on neuronal survival and functional recovery in vivo. Western blotting (WB), immunofluorescence (IF), and enzyme-linked immunosorbent assay (ELISA) were used to detect the expression levels of NLRP3 inflammasome and autophagy-related proteins. Transmission electron microscopy (TEM) was used to confirm the occurrence of zinc-induced autophagy. In vitro, lipopolysaccharide (LPS) and ATP polarized BV2 cells to a proinflammatory phenotype. 3-Methyladenine (3-MA) and bafilomycin A1 (BafA1) were chosen to explore the relationship between the NLRP3 inflammasome and autophagy. A coimmunoprecipitation assay was used to detect the ubiquitination of the NLRP3 protein. RESULTS Our data showed that zinc significantly promoted motor function recovery after SCI. In vivo, zinc treatment inhibited the protein expression level of NLRP3 while increasing the level of autophagy. These effects were fully validated by the polarization of BV2 cells to a proinflammatory phenotype. The results showed that when 3-MA and BafA1 were applied, the promotion of autophagy by zinc was blocked and that the inhibitory effect of zinc on NLRP3 was reversed. Furthermore, co-IP confirmed that the promotion of autophagy by zinc also activated the protein expression of ubiquitin and suppressed high levels of NLRP3. CONCLUSION Zinc provides neuroprotection by regulating NLRP3 inflammasome through autophagy and ubiquitination after SCI.
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Affiliation(s)
- Jia‐quan Lin
- Department of OrthopedicsThe First Affiliated Hospital of Jinzhou Medical UniversityJinzhouChina
| | - He Tian
- Department of Histology and EmbryologyJinzhou Medical UniversityJinzhouChina
| | - Xiao‐guang Zhao
- Department of EmergencyThe First Affifiliated Hospital of Jinzhou Medical UniversityJinzhouChina
| | - Sen Lin
- Department of OrthopedicsThe First Affiliated Hospital of Jinzhou Medical UniversityJinzhouChina
| | - Dao‐yong Li
- Department of OrthopedicsThe First Affiliated Hospital of Jinzhou Medical UniversityJinzhouChina
| | - Yuan‐ye Liu
- Department of OrthopedicsThe First Affiliated Hospital of Jinzhou Medical UniversityJinzhouChina
| | - Chang Xu
- Department of OrthopedicsThe First Affiliated Hospital of Jinzhou Medical UniversityJinzhouChina
| | - Xi‐fan Mei
- Department of OrthopedicsThe First Affiliated Hospital of Jinzhou Medical UniversityJinzhouChina
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Sánchez J, Montilla M, Gutiérrez-Panizo C, Sotillo J, Fuentes P, Montes A, Gutiérrez AM. Analytical characterization of trace elements (zinc, copper, cadmium, lead and selenium) in saliva of pigs under common pathological conditions in the field: a pilot study. BMC Vet Res 2020; 16:27. [PMID: 32000745 PMCID: PMC6993390 DOI: 10.1186/s12917-020-2245-6] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2019] [Accepted: 01/16/2020] [Indexed: 01/05/2023] Open
Abstract
Background This study is focused on the measurement of trace elements (zinc, copper, cadmium, lead and selenium) in the saliva of pigs in order to study their levels on different porcine pathological conditions in the field. The experiment involved 15 pigs without clinical signs of disease and 42 diseased pigs (suffering from lameness, rectal prolapse, fatigue or growth rate retardation). Individual saliva samples were collected, allowing the pigs to chew a sponge each for trace element quantifications through atomic absorption spectrometry (AAS). Since this is the first report on the measurements of trace elements in porcine saliva, a routine analytical validation study was performed for the quantification of all the studied elements. Moreover, the acute phase proteins C-reactive protein (CRP) and haptoblobin (Hp), the total antioxidant capacity (TAC) and adenosine deaminase (ADA) were quantified in the saliva samples for the animal’s health status assessment. Results Modifications in the levels of acute phase proteins or ADA were only recorded in animals with lameness and rectal prolapse and those with fatigue respectively. Moreover, TAC level changes were observed in pigs with growth-rate retardation. However, alterations in the levels of two or more trace elements were reported for all the different groups of diseased pigs with evident variations within pathologies. Conclusions The salivary quantification of trace elements could be considered as a complementary tool to acute phase proteins, TAC and ADA determinations for disease detection and differentiation in the pig and should be explored in greater depth.
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Affiliation(s)
- Jorge Sánchez
- BioVetMed Research Group, Department of Animal Medicine and Surgery, Veterinary School, University of Murcia, Espinardo, 30100, Murcia, Spain.,Cefu S.A., 30840, Alhama de Murcia, Murcia, Spain
| | - Miguel Montilla
- BioVetMed Research Group, Department of Animal Medicine and Surgery, Veterinary School, University of Murcia, Espinardo, 30100, Murcia, Spain
| | - Cándido Gutiérrez-Panizo
- BioVetMed Research Group, Department of Animal Medicine and Surgery, Veterinary School, University of Murcia, Espinardo, 30100, Murcia, Spain
| | - Juan Sotillo
- BioVetMed Research Group, Department of Animal Medicine and Surgery, Veterinary School, University of Murcia, Espinardo, 30100, Murcia, Spain
| | - Pablo Fuentes
- BioVetMed Research Group, Department of Animal Medicine and Surgery, Veterinary School, University of Murcia, Espinardo, 30100, Murcia, Spain.,Cefu S.A., 30840, Alhama de Murcia, Murcia, Spain
| | - Ana Montes
- BioVetMed Research Group, Department of Animal Medicine and Surgery, Veterinary School, University of Murcia, Espinardo, 30100, Murcia, Spain
| | - Ana María Gutiérrez
- BioVetMed Research Group, Department of Animal Medicine and Surgery, Veterinary School, University of Murcia, Espinardo, 30100, Murcia, Spain.
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Abstract
Metals are essential components in all forms of life required for the function of nearly half of all enzymes and are critically involved in virtually all fundamental biological processes. Especially, the transition metals iron (Fe), zinc (Zn), manganese (Mn), nickel (Ni), copper (Cu) and cobalt (Co) are crucial micronutrients known to play vital roles in metabolism as well due to their unique redox properties. Metals carry out three major functions within metalloproteins: to provide structural support, to serve as enzymatic cofactors, and to mediate electron transportation. Metal ions are also involved in the immune system from metal allergies to nutritional immunity. Within the past decade, much attention has been drawn to the roles of metal ions in the immune system, since increasing evidence has mounted to suggest that metals are critically implicated in regulating both the innate immune sensing of and the host defense against invading pathogens. The importance of ions in immunity is also evidenced by the identification of various immunodeficiencies in patients with mutations in ion channels and transporters. In addition, cancer immunotherapy has recently been conclusively demonstrated to be effective and important for future tumor treatment, although only a small percentage of cancer patients respond to immunotherapy because of inadequate immune activation. Importantly, metal ion-activated immunotherapy is becoming an effective and potential way in tumor therapy for better clinical application. Nevertheless, we are still in a primary stage of discovering the diverse immunological functions of ions and mechanistically understanding the roles of these ions in immune regulation. This review summarizes recent advances in the understanding of metal-controlled immunity. Particular emphasis is put on the mechanisms of innate immune stimulation and T cell activation by the essential metal ions like calcium (Ca2+), zinc (Zn2+), manganese (Mn2+), iron (Fe2+/Fe3+), and potassium (K+), followed by a few unessential metals, in order to draw a general diagram of metalloimmunology.
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Affiliation(s)
- Chenguang Wang
- Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education, School of Life Sciences, Peking University, Beijing, China; Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China
| | - Rui Zhang
- Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education, School of Life Sciences, Peking University, Beijing, China; Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China
| | - Xiaoming Wei
- Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education, School of Life Sciences, Peking University, Beijing, China; Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China
| | - Mengze Lv
- Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education, School of Life Sciences, Peking University, Beijing, China; Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China
| | - Zhengfan Jiang
- Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education, School of Life Sciences, Peking University, Beijing, China; Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China.
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Paulazo MA, Klecha AJ, Sterle HA, Valli E, Torti H, Cayrol F, Barreiro Arcos ML, Cremaschi GA. Hypothyroidism-related zinc deficiency leads to suppression of T lymphocyte activity. Endocrine 2019; 66:266-277. [PMID: 31056723 DOI: 10.1007/s12020-019-01936-7] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2019] [Accepted: 04/11/2019] [Indexed: 12/15/2022]
Abstract
PURPOSE Hypothyroidism has been shown to induce immunosuppression and both the thyroid status and immunity are affected by zinc deficiency. However, the impact of hypothyroidism on zinc metabolism and its possible relationship with the immune status has not yet been deeply explored. Here, our aim was to study whether hypothyroidism may alter zinc metabolism and thus lead to the impairment of T lymphocyte activity. METHODS Variations in the distribution of zinc in the body were evaluated in PTU-treated hypothyroid mice. The effects of hypothyroidism and zinc deficiency were studied on T lymphocyte proliferation after stimulation both in vitro and in vivo. For in vitro assays, thyroid hormone-free or zinc chelator (TPEN or DTPA)-supplemented media were used. For in vivo assays, lymphocyte activity was evaluated in cells from hypothyroid, T3-treated, and zinc-supplemented mice. RESULTS Hypothyroid mice showed lower levels of zinc in femur and lymph nodes than controls. T3 and zinc supplementation reversed these effects. In vitro, both thyroid hormone and zinc deficiency led to a decreased response to mitogen stimulation. However, only zinc deficiency was able to induce lymphocyte apoptosis. Mitogen-stimulated T cells from hypothyroid mice showed impaired proliferation, accompanied by decreased activation of PKC and lower levels of p-ERK, effects that were reversed by T3 replacement or zinc supplementation. CONCLUSIONS Our results show an important role of zinc deficiency in hypothyroid-mediated T-cell suppression and suggest the importance of evaluating zinc levels and restoring them when necessary to maintain an efficient immune response in hypothyroid patients.
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Affiliation(s)
- María Alejandra Paulazo
- Instituto de Investigaciones Biomédicas (BIOMED), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Facultad de Ciencias Médicas, Pontificia Universidad Católica Argentina (UCA), Av. Alicia Moreau de Justo 1600, 3er piso (1107 AAZ), Buenos Aires, Argentina
| | - Alicia Juana Klecha
- Instituto de Investigaciones Biomédicas (BIOMED), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Facultad de Ciencias Médicas, Pontificia Universidad Católica Argentina (UCA), Av. Alicia Moreau de Justo 1600, 3er piso (1107 AAZ), Buenos Aires, Argentina
- Cátedra de Física, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina
| | - Helena Andrea Sterle
- Instituto de Investigaciones Biomédicas (BIOMED), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Facultad de Ciencias Médicas, Pontificia Universidad Católica Argentina (UCA), Av. Alicia Moreau de Justo 1600, 3er piso (1107 AAZ), Buenos Aires, Argentina
| | - Eduardo Valli
- Instituto de Investigaciones Biomédicas (BIOMED), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Facultad de Ciencias Médicas, Pontificia Universidad Católica Argentina (UCA), Av. Alicia Moreau de Justo 1600, 3er piso (1107 AAZ), Buenos Aires, Argentina
| | - Horacio Torti
- Cátedra de Física, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina
| | - Florencia Cayrol
- Instituto de Investigaciones Biomédicas (BIOMED), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Facultad de Ciencias Médicas, Pontificia Universidad Católica Argentina (UCA), Av. Alicia Moreau de Justo 1600, 3er piso (1107 AAZ), Buenos Aires, Argentina
| | - María Laura Barreiro Arcos
- Instituto de Investigaciones Biomédicas (BIOMED), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Facultad de Ciencias Médicas, Pontificia Universidad Católica Argentina (UCA), Av. Alicia Moreau de Justo 1600, 3er piso (1107 AAZ), Buenos Aires, Argentina
| | - Graciela Alicia Cremaschi
- Instituto de Investigaciones Biomédicas (BIOMED), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Facultad de Ciencias Médicas, Pontificia Universidad Católica Argentina (UCA), Av. Alicia Moreau de Justo 1600, 3er piso (1107 AAZ), Buenos Aires, Argentina.
- Cátedra de Física, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina.
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Wessels I, Rink L. Micronutrients in autoimmune diseases: possible therapeutic benefits of zinc and vitamin D. J Nutr Biochem 2019; 77:108240. [PMID: 31841960 DOI: 10.1016/j.jnutbio.2019.108240] [Citation(s) in RCA: 42] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2019] [Accepted: 09/09/2019] [Indexed: 12/14/2022]
Abstract
A functional immune system is essential for healthy life. This is achieved by the coordinate activation and interaction of different immune cells. One should be aware that activation of the immune response is as important as its deactivation when the pathogens are cleared, as otherwise host tissue can be damaged up to life-threatening levels. Autoimmune diseases (AID) represent a phenomenon of immune cells attacking host cells and tissue. Five to eight percent of the world's population are currently affected by 80-100 AID. In recent years, the incidence has been constantly increasing, reaching alarmingly high numbers particularly for type 1 diabetes mellitus, Crohn's disease, rheumatoid arthritis, Sjogren's syndrome and multiple sclerosis. This indicates a higher societal burden of AID for the future. This article provides an overview of general concepts of triggers and underlying mechanisms leading to self-destruction. Lately, several original concepts of disease etiology were revised, and there is a variety of hypotheses on triggers, underlying mechanisms and preventive actions. This article concentrates on the importance of nutrition, especially zinc and vitamin D, for balancing the immune function. Homespun nutritional remedies seem to reenter today's therapeutic strategies. Current treatment approaches are largely symptomatic or suppress the immune system. However, recent studies reveal significant benefits of nutrition-related therapeutic approaches including prevention and treatment of established disease, which offer a cost-efficient and trigger-unspecific alternative addressing balancing rather than suppression of the immune system. Zinc and vitamin D are currently the best studied and most promising candidates for therapeutic intervention.
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Affiliation(s)
- Inga Wessels
- Institute of Immunology, Medical Faculty, RWTH Aachen University, Pauwelsstr. 30, D-52074 Aachen, Germany.
| | - Lothar Rink
- Institute of Immunology, Medical Faculty, RWTH Aachen University, Pauwelsstr. 30, D-52074 Aachen, Germany.
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17
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Burián Z, Ladányi A, Barbai T, Piurkó V, Garay T, Rásó E, Tímár J. Selective Inhibition of HIF1α Expression by ZnSO 4 Has Antitumoral Effects in Human Melanoma. Pathol Oncol Res 2019; 26:673-679. [PMID: 30613921 DOI: 10.1007/s12253-018-00573-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2018] [Accepted: 12/21/2018] [Indexed: 10/27/2022]
Abstract
Zinc as an essential trace metal is a ubiquitous component of various molecules of the cell. Studies indicated that it may modulate functions of various cancer cell types, and can even inhibit metastasis formation in experimental models. In melanoma, zinc was shown to affect melanin production and to induce apoptosis. Using human melanoma cell lines, we have tested the effects of ZnSO4 on cell proliferation, survival, migration as well as in vivo on experimental liver colony formation. We have found that ZnSO4 has antiproliferative and proapoptotic effects in vitro. In SCID mice intraperitoneal administration of ZnSO4 specifically inhibited liver colony formation without affecting primary tumor growth. To reveal the molecular mechanisms of action of zinc in human melanoma, we have tested mRNA expression of zinc finger transcription factors and found a strong inhibitory effect on HIF1α, as compared to WT1 whereas HIF2α and MTF1 expression was unaffected. Immunohistochemical detection of HIF1α protein in liver metastases confirmed its decreased nuclear expression after in vivo ZnSO4 treatment. These data indicate that in human melanoma zinc administration may have an antimetastatic effect due to a selective downregulation of HIF1α.
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Affiliation(s)
- Z Burián
- National Institute of Oncology, Budapest, Hungary
| | - A Ladányi
- National Institute of Oncology, Budapest, Hungary
| | - T Barbai
- 2nd Department of Pathology, Semmelweis University, Üllői út 93., Budapest, H-1091, Hungary
| | - V Piurkó
- 2nd Department of Pathology, Semmelweis University, Üllői út 93., Budapest, H-1091, Hungary
| | - T Garay
- 2nd Department of Pathology, Semmelweis University, Üllői út 93., Budapest, H-1091, Hungary
| | - E Rásó
- 2nd Department of Pathology, Semmelweis University, Üllői út 93., Budapest, H-1091, Hungary
| | - József Tímár
- 2nd Department of Pathology, Semmelweis University, Üllői út 93., Budapest, H-1091, Hungary.
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18
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Jarosz Ł, Marek A, Grądzki Z, Laskowska E, Kwiecień M. Effect of Zinc Sulfate and Zinc Glycine Chelate on Concentrations of Acute Phase Proteins in Chicken Serum and Liver Tissue. Biol Trace Elem Res 2019; 187:258-272. [PMID: 29675569 PMCID: PMC6314988 DOI: 10.1007/s12011-018-1346-6] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2018] [Accepted: 04/10/2018] [Indexed: 01/13/2023]
Abstract
The aim of the study was to determine how inorganic and organic forms of zinc affect the concentrations of C-reactive protein (CRP), serum amyloid A (SAA), alpha-1-acid glycoprotein (α-1-AGP), haptoglobin (Hp), and transferrin (TRF) in the blood and liver tissue of 450 1-day-old Ross 308 chicken. Four experimental groups received one the following: inorganic zinc (ZnSO4), a zinc phytase enzyme supplement (ZnSO4-F), organic zinc in combination with glycine (Zn-Gly), or organic zinc supplemented with phytase (Zn-Gly-F). The chicken serum and liver homogenates were assayed using an ELISA kit. The results of the study showed statistically significantly higher serum and liver concentration of SAA in the group of birds that received zinc sulfate in comparison to the group of birds receiving zinc in organic form. A statistically significantly higher serum concentration of CRP and α-1-AGP was also noted in the group receiving zinc sulfate as compared to the Zn-Gly group. Comparison of the serum concentration of TRF between the supplemented groups showed a statistically significant increase in this parameter in the Zn-Gly-F group as compared to the ZSO4-F group. The increase in the serum concentration of Hp in all groups in comparison to the control may indicate stimulation of local immune mechanisms. The results of this study showed an increase in the concentrations of APPs such as AGP and TRF following the administration of zinc glycine chelates, which may demonstrate their effect on metabolic processes in the liver and on immunocompetent cells that regulate the intensity of the immune response.
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Affiliation(s)
- Łukasz Jarosz
- Department of Epizootiology and Clinic of Infectious Diseases, Faculty of Veterinary Medicine, University of Life Sciences in Lublin, Głęboka 30, 20-612 Lublin, Poland
| | - Agnieszka Marek
- Sub-Department of Preventive Veterinary and Avian Diseases, Institute of Biological Bases of Animal Diseases, Faculty of Veterinary Medicine, University of Life Sciences in Lublin, Głęboka 30, 20-612 Lublin, Poland
| | - Zbigniew Grądzki
- Department of Epizootiology and Clinic of Infectious Diseases, Faculty of Veterinary Medicine, University of Life Sciences in Lublin, Głęboka 30, 20-612 Lublin, Poland
| | - Ewa Laskowska
- Department of Epizootiology and Clinic of Infectious Diseases, Faculty of Veterinary Medicine, University of Life Sciences in Lublin, Głęboka 30, 20-612 Lublin, Poland
| | - Małgorzata Kwiecień
- Faculty of Biology and Animal Breeding, Institute of Animal Nutrition and Bromatology, Department of Animal Nutrition, University of Life Sciences in Lublin, Akademicka 13, 20-950 Lublin, Poland
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19
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Liu W, Li J, Cheng M, Wang Q, Yeung KWK, Chu PK, Zhang X. Zinc-Modified Sulfonated Polyetheretherketone Surface with Immunomodulatory Function for Guiding Cell Fate and Bone Regeneration. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2018; 5:1800749. [PMID: 30356934 PMCID: PMC6193167 DOI: 10.1002/advs.201800749] [Citation(s) in RCA: 164] [Impact Index Per Article: 23.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/15/2018] [Revised: 06/19/2018] [Indexed: 05/19/2023]
Abstract
The cytokines released by immune cells are considered important factors to induce bone tissue regeneration. However, the pathway of those bone-targeting macrophage cytokines induced by biomaterial surface under tissue microenvironment is rarely reported. In this study, the immunomodulatory capability of zinc ions on macrophage polarization and its effects on osteogenic differentiation are investigated. Hence, a layer of zinc ions are incorporated on sulfonated polyetheretherketone (SPEEK) biomaterials by using a customized magnetron sputtering technique. The results reveal that the microenvironment on Zn-coated SPEEK can modulate nonactivated macrophage polarization to an anti-inflammatory phenotype and induce the secretion of anti-inflammatory and osteogenic cytokines. The osteogenic differentiation capability of bone marrow stromal cells (BMSCs) is therefore enhanced, leading to improved osteointegration between the zinc-coated SPEEK and bone tissue. This study verifies that zinc ion is a promising additive in the osteoimmunomodulation process and provides knowledge that may pave the way to develop the next generation of immunomodulatory biomaterials.
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Affiliation(s)
- Wei Liu
- Department of OrthopaedicsShanghai Jiao Tong University Affiliated Sixth People's HospitalShanghai Jiao Tong UniversityShanghai200233China
| | - Jinhua Li
- Department of Orthopaedics and TraumatologyLi Ka Shing Faculty of MedicineThe University of Hong KongPokfulamHong Kong999077China
- Department of Physics and Department of Materials Science and EngineeringCity University of Hong KongTat Chee AvenueKowloonHong Kong999077China
| | - Mengqi Cheng
- Department of OrthopaedicsShanghai Jiao Tong University Affiliated Sixth People's HospitalShanghai Jiao Tong UniversityShanghai200233China
| | - Qiaojie Wang
- Department of OrthopaedicsShanghai Jiao Tong University Affiliated Sixth People's HospitalShanghai Jiao Tong UniversityShanghai200233China
| | - Kelvin W. K. Yeung
- Department of Orthopaedics and TraumatologyLi Ka Shing Faculty of MedicineThe University of Hong KongPokfulamHong Kong999077China
| | - Paul K. Chu
- Department of Physics and Department of Materials Science and EngineeringCity University of Hong KongTat Chee AvenueKowloonHong Kong999077China
| | - Xianlong Zhang
- Department of OrthopaedicsShanghai Jiao Tong University Affiliated Sixth People's HospitalShanghai Jiao Tong UniversityShanghai200233China
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20
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Combined Treatment with Zinc Aspartate and Intravenous Immunoglobulins (IVIGs) Ameliorates Experimental Autoimmune Encephalomyelitis (EAE). J Immunol Res 2018; 2018:5982169. [PMID: 30356433 PMCID: PMC6178489 DOI: 10.1155/2018/5982169] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2018] [Revised: 08/17/2018] [Accepted: 09/02/2018] [Indexed: 11/18/2022] Open
Abstract
Intravenous immunoglobulins (IVIGs) are widely used in replacement therapy of primary and secondary immunodeficiency disorders and in approved autoimmune indications. In addition, IVIG application is used off-label for treatment of other autoimmune diseases, e.g., multiple sclerosis (MS), an inflammatory autoimmune disorder with a clear T cell-mediated immune pathogenesis. The trace element zinc is shown to play a regulatory role in the maintenance of immune functions. Changes of zinc homeostasis affect both the innate and the adaptive immune system. On one hand, therapeutic zinc supplementation can normalize impaired immune functions due to zinc deficiency. On the other hand, therapeutic zinc supplementation is under consideration as a possible option to treat T cell-mediated autoimmune diseases. The aim of the present study was to investigate the influence of IVIG (Octagam®), zinc aspartate (Unizink®), and the combined application of both preparations in the experimental autoimmune encephalomyelitis (EAE), the animal model of MS. Therapeutic intraperitoneal application of zinc aspartate significantly diminished clinical signs during the relapsing-remitting phase of EAE in SJL/J mice. In contrast, IVIG given in a therapeutic manner did not influence the course of EAE. Interestingly, the combined application of both, IVIG and zinc aspartate, significantly reduced the severity of the disease during the acute and the relapsing-remitting phase of the EAE. Our data suggest that the combination of IVIG and zinc aspartate may have beneficial effects in autoimmune diseases, like MS. Further studies should verify the benefit of a controlled immunosuppressive therapy with IVIG and zinc for such diseases.
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Mao SY, Lien TF. Effects of nanosized zinc oxide and γ-polyglutamic acid on eggshell quality and serum parameters of aged laying hens. Arch Anim Nutr 2017; 71:373-383. [DOI: 10.1080/1745039x.2017.1355600] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Affiliation(s)
- Syuan-Yian Mao
- Department of Animal Science, National Chiayi University, Chiayi, Taiwan
| | - Tu-Fa Lien
- Department of Animal Science, National Chiayi University, Chiayi, Taiwan
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22
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Sheikh AA, Aggarwal A, B I, Aarif O. Inorganic zinc supplementation modulates heat shock and immune response in heat stressed peripheral blood mononuclear cells of periparturient dairy cows. Theriogenology 2017; 95:75-82. [PMID: 28460683 DOI: 10.1016/j.theriogenology.2017.02.024] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2016] [Revised: 02/23/2017] [Accepted: 02/27/2017] [Indexed: 10/20/2022]
Abstract
Thermal stress in India is one of the major constraints affecting dairy cattle productivity. Every attempt should be made to ameliorate the heat and calving related stress in high producing dairy cows for higher economic returns. In the current study, inorganic zinc was tried to alleviate the adverse effects of thermal stress in periparturient cows. Twelve cows, six each of Sahiwal and Karan Fries (KF) in their second parity with confirmed pregnancy were chosen for the experiment. The blood samples were collected periparturiently on three occasions viz. -21, 0 and +21 days relative to calving. The in vitro study was conducted after isolating peripheral blood mononuclear cells (PBMC) from whole blood. The cultured PBMC were subjected to three different levels of exposures viz. 37°C as control, 42°C to induce thermal stress and 42°C + zinc to ameliorate the adverse effects of high temperature. Heat shock lead to a significant (P<0.05) rise in the level of heat shock proteins (HSP). HSP was more on the day of calving as well. KF showed more HSP concentration than Sahiwal breed indicating the heat bearing capacity of later. Zinc treatment to thermally stressed PBMC caused a fall in the HSP concentration in both the breeds during periparturient period. Moreover, heat stress increased significantly (P<0.05) the Interleukin 6 (IL-6) concentration which declined upon zinc supplementation to PBMC. IL-6 levels decreased periparturiently. Heat and calving related stress caused a fall in the IL-12 levels which increased significantly (P<0.05) with zinc supplementation. These findings suggest that zinc supplementation attenuates the HSP response and augments immunity in PBMC of periparturient dairy cows. The study could help to alleviate the heat stress and potentiate immunity by providing mineral supplements in periparturient dairy cattle habituating tropics.
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Affiliation(s)
- Aasif Ahmad Sheikh
- Animal Physiology Division, ICAR-National Dairy Research Institute, Karnal, Haryana, India.
| | - Anjali Aggarwal
- Animal Physiology Division, ICAR-National Dairy Research Institute, Karnal, Haryana, India
| | - Indu B
- Division of Physiology & Climatology, ICAR-Indian Veterinary Research Institute, Izatnagar, Uttar Pradesh, India
| | - Ovais Aarif
- Animal Physiology Division, ICAR-National Dairy Research Institute, Karnal, Haryana, India
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23
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Hasanzadeh Kiabi F, Alipour A, Darvishi-Khezri H, Aliasgharian A, Emami Zeydi A. Zinc Supplementation in Adult Mechanically Ventilated Trauma Patients is Associated with Decreased Occurrence of Ventilator-associated Pneumonia: A Secondary Analysis of a Prospective, Observational Study. Indian J Crit Care Med 2017; 21:34-39. [PMID: 28197049 PMCID: PMC5278588 DOI: 10.4103/0972-5229.198324] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Ventilator-associated pneumonia (VAP) is a type of lung infection that typically affects critically ill patients undergoing mechanical ventilation (MV) in the Intensive Care Unit (ICU). The aim of this analysis is to determine potential association between zinc supplementation with the occurrence of VAP in adult mechanically ventilated trauma patients. SUBJECTS AND METHODS This secondary analysis of a prospective observational study was carried out over a period of 1 year in ICUs of one teaching hospital in Iran. A total of 186 adults mechanically ventilated trauma patients, who required at least 48 h of MV and received zinc sulfate supplement (n = 82) or not (n = 104) during their ICU stay, were monitored for the occurrence of VAP until their discharge from the ICU or death. RESULTS Forty-one of 186 patients developed VAP, 29.09 days after admission (95% confidence interval [CI]: 26.27-31.9). The overall incidence of VAP was 18.82 cases per 1000 days of intubation (95% CI: 13.86-25.57). Patients who received zinc sulfate supplement have smaller hazard of progression to VAP than others (hazard ratio: 0.318 [95% CI: 0.138-0.732]; P < 0.0001). CONCLUSION The findings show that zinc supplementation may be associated with a significant reduction in the occurrence of VAP in adult mechanically ventilated trauma patients. Further well-designed randomized clinical trials to confirm the efficacy of this potential preventive modality are warranted.
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Affiliation(s)
- Farshad Hasanzadeh Kiabi
- Department of Anesthesiology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
| | - Abbas Alipour
- Department of Community Medicine, Mazandaran University of Medical Sciences, Sari, Iran
| | | | - Aily Aliasgharian
- Student Research Committee, Thalassemia Research Center, Hemoglobinopathy Institute, Mazandaran University of Medical Sciences, Sari, Iran
| | - Amir Emami Zeydi
- Student Research Committee, Department of Medical-Surgical Nursing, School of Nursing and Midwifery, Mashhad University of Medical Sciences, Mashhad, Iran
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Jarosz Ł, Marek A, Grądzki Z, Kwiecień M, Kalinowski M. The effect of feed supplementation with zinc chelate and zinc sulphate on selected humoral and cell-mediated immune parameters and cytokine concentration in broiler chickens. Res Vet Sci 2016; 112:59-65. [PMID: 28126602 DOI: 10.1016/j.rvsc.2016.09.007] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2016] [Accepted: 09/12/2016] [Indexed: 10/21/2022]
Abstract
The ability of poultry to withstand infectious disease caused by bacteria, viruses or protozoa depends upon the integrity of the immune system. Zinc is important for proper functioning of heterophils, mononuclear phagocytes and T lymphocytes. Numerous data indicate that the demand for zinc in poultry is not met in Poland due to its low content in feeds of vegetable origin. The aim of the study was to determine the effect of supplementation of inorganic (ZnSO4 and ZnSO4+ phytase enzyme), and organic forms of zinc (Zn with glycine and Zn with glycine and phytase enzyme) on selected parameters of the cellular and humoral immune response in broiler chickens by evaluating the percentage of CD3+CD4+, CD3+CD8+, CD25+, MHC Class II, and BU-1+ lymphocytes, the phagocytic activity of monocytes and heterophils, and the concentration of IL-2, IL-10 and TNF-α in the peripheral blood. Flow cytometry was used to determine selected cell-mediated immune response parameters. Phagocytic activity in whole blood was performed using the commercial Phagotest kit (ORPEGEN-Pharma, Immuniq, Poland). The results showed that supplementation with zinc chelates causes activation of the cellular and humoral immune response in poultry, helping to maintain the balance between the Th1 and Th2 response and enhancing resistance to infections. In contrast with chelates, the use of zinc in the form of sulphates has no immunomodulatory effect and may contribute to the development of local inflammatory processes in the digestive tract, increasing susceptibility to infection.
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Affiliation(s)
- Łukasz Jarosz
- Department of Epizootiology and Clinic of Infectious Diseases, Faculty of Veterinary Medicine, University of Life Sciences in Lublin, Głęboka 30, 20-612 Lublin, Poland.
| | - Agnieszka Marek
- Department of Epizootiology and Clinic of Infectious Diseases, Faculty of Veterinary Medicine, University of Life Sciences in Lublin, Głęboka 30, 20-612 Lublin, Poland; Department of Veterinary Prevention and Avian Diseases, Institute of Biological Bases of Animal Diseases, Faculty of Veterinary Medicine, University of Life Sciences in Lublin, Głęboka 30, 20-612 Lublin, Poland
| | - Zbigniew Grądzki
- Department of Epizootiology and Clinic of Infectious Diseases, Faculty of Veterinary Medicine, University of Life Sciences in Lublin, Głęboka 30, 20-612 Lublin, Poland
| | - Małgorzata Kwiecień
- Department of Epizootiology and Clinic of Infectious Diseases, Faculty of Veterinary Medicine, University of Life Sciences in Lublin, Głęboka 30, 20-612 Lublin, Poland; Faculty of Biology and Animal Breeding, Institute of Animal Nutrition and Bromatology, Department of Animal Nutrition, University of Life Sciences in Lublin, Akademicka 13, 20-950 Lublin, Poland
| | - Marcin Kalinowski
- Department of Epizootiology and Clinic of Infectious Diseases, Faculty of Veterinary Medicine, University of Life Sciences in Lublin, Głęboka 30, 20-612 Lublin, Poland
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Abstract
In 2012 there were 135,943 infants of multiple pregnancies born in the United States, nearly a 2-fold increase since 1980, with twins accounting for 96% of all multiple births. To date, most perinatal morbidities associated with multiple births have proven resistant to technological or pharmaceutical interventions. Maternal nutrition can have a profound effect on the course and outcome of multiple pregnancy, with the goal of achieving optimal intrauterine growth and birthweights, and minimizing prenatal and perinatal complications for the mother and her children.
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Affiliation(s)
- Barbara Luke
- Michigan State University College of Human Medicine, East Lansing, Michigan
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26
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Maares M, Haase H. Zinc and immunity: An essential interrelation. Arch Biochem Biophys 2016; 611:58-65. [PMID: 27021581 DOI: 10.1016/j.abb.2016.03.022] [Citation(s) in RCA: 195] [Impact Index Per Article: 21.7] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2016] [Revised: 03/16/2016] [Accepted: 03/23/2016] [Indexed: 12/27/2022]
Abstract
The significance of the essential trace element zinc for immune function has been known for several decades. Zinc deficiency affects immune cells, resulting in altered host defense, increased risk of inflammation, and even death. The micronutrient zinc is important for maintenance and development of immune cells of both the innate and adaptive immune system. A disrupted zinc homeostasis affects these cells, leading to impaired formation, activation, and maturation of lymphocytes, disturbed intercellular communication via cytokines, and weakened innate host defense via phagocytosis and oxidative burst. This review outlines the connection between zinc and immunity by giving a survey on the major roles of zinc in immune cell function, and their potential consequences in vivo.
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Affiliation(s)
- Maria Maares
- Department of Food Chemistry and Toxicology, Berlin Institute of Technology, Gustav-Meyer-Allee 25, D-13355 Berlin, Germany
| | - Hajo Haase
- Department of Food Chemistry and Toxicology, Berlin Institute of Technology, Gustav-Meyer-Allee 25, D-13355 Berlin, Germany.
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Tsai Y, Mao S, Li M, Huang J, Lien T. Effects of nanosize zinc oxide on zinc retention, eggshell quality, immune response and serum parameters of aged laying hens. Anim Feed Sci Technol 2016. [DOI: 10.1016/j.anifeedsci.2016.01.009] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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Li MZ, Huang JT, Tsai YH, Mao SY, Fu CM, Lien TF. Nanosize of zinc oxide and the effects on zinc digestibility, growth performances, immune response and serum parameters of weanling piglets. Anim Sci J 2016; 87:1379-1385. [PMID: 26805551 DOI: 10.1111/asj.12579] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2015] [Revised: 10/07/2015] [Accepted: 11/04/2015] [Indexed: 11/28/2022]
Abstract
The aim of this study was to investigate the effect of dietary supplementation of nanosize zinc on zinc digestibility, growth performances, immune response and serum parameters of weanling piglets. Ninety-six LYD weanling piglets were assigned to control, zinc oxide (ZnO), organic-Zn (Zn-methionine) and nanosize ZnO (nano-Zn) groups with four replicates. The zinc was at the 120 mg/kg level in the treatment group's diet, while the control group's was 80 mg/kg Zn. The experiment results indicated that the nano-Zn and organic-Zn groups had significantly higher Zn digestibility compared to the ZnO and control groups. For the immune response traits, the IgG level and goat red blood cells (GRBC) antibody titer were nano-Zn and organic-Zn>ZnO>control; in the phytohemagglutinin (PHA) challenge test result, nano-Zn>organic-Zn>ZnO>control; in regard to the γ-globulin level, nano-Zn and organic-Zn>ZnO and control, with significant difference between groups. In the serum parameters aspect, serum Zn concentration in nano-Zn and organic-Zn groups were higher than in the ZnO and control groups, serum growth hormone concentration was increased in the nano-Zn group than in the other groups. In conclusion, nanosize zinc oxide for dietary supplementation can increase zinc digestibility, serum growth hormone levels and carbonic anhydrase activity and enhance the immune response of weanling piglets.
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Affiliation(s)
- Ming-Zhe Li
- Department of Animal Science, National Chiayi University, Chiayi, Taiwan
| | - Jie-Ting Huang
- Department of Animal Science, National Chiayi University, Chiayi, Taiwan
| | - Yi-Hao Tsai
- Department of Animal Science, National Chiayi University, Chiayi, Taiwan
| | - Syuan-Yian Mao
- Department of Animal Science, National Chiayi University, Chiayi, Taiwan
| | - Chao-Ming Fu
- Department of Physics, National Taiwan University, Taipei, Taiwan
| | - Tu-Fa Lien
- Department of Animal Science, National Chiayi University, Chiayi, Taiwan.
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29
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Oxidative stress and age-related changes in T cells: is thalassemia a model of accelerated immune system aging? Cent Eur J Immunol 2016; 41:116-24. [PMID: 27095931 PMCID: PMC4829813 DOI: 10.5114/ceji.2015.56973] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2015] [Accepted: 07/20/2015] [Indexed: 12/21/2022] Open
Abstract
Iron overload in β-thalassemia major occurs mainly due to blood transfusion, an essential treatment for β-thalassemia major patients, which results in oxidative stress. It has been thought that oxidative stress causes elevation of immune system senescent cells. Under this condition, cells normally enhance in aging, which is referred to as premature immunosenescence. Because there is no animal model for immunosenescence, most knowledge on the immunosenescence pattern is based on induction of immunosenescence. In this review, we describe iron overload and oxidative stress in β-thalassemia major patients and how they make these patients a suitable human model for immunosenescence. We also consider oxidative stress in some kinds of chronic virus infections, which induce changes in the immune system similar to β-thalassemia major. In conclusion, a therapeutic approach used to improve the immune system in such chronic virus diseases, may change the immunosenescence state and make life conditions better for β-thalassemia major patients.
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Shi L, Zhang L, Li C, Hu X, Wang X, Huang Q, Zhou G. Dietary zinc deficiency impairs humoral and cellular immune responses to BCG and ESAT-6/CFP-10 vaccination in offspring and adult rats. Tuberculosis (Edinb) 2016; 97:86-96. [PMID: 26980500 DOI: 10.1016/j.tube.2016.01.002] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2015] [Revised: 01/08/2016] [Accepted: 01/11/2016] [Indexed: 10/22/2022]
Abstract
BACKGROUND Besides being the world's most widely used vaccine, BCG is the most controversial vaccine in current use. Estimates of protection impaired by BCG against pulmonary TB vary from nil to 80%. Dietary zinc deficiency has been confirmed to impair the immune function of animals. However, knowledge about effects of mild dietary zinc deficiency and the time of vaccination on BCG vaccine responsiveness in offspring and adult rats is limited. This work investigated the consequences of feeding zinc deficient and normal zinc diets to rats during gestation, infancy or adulthood on the immune responses to BCG vaccination. METHODS On gestation day 0, sixteen maternal rats were divided into two groups and fed with diets bellow: a control diet ad libitum (30 μg zinc/g diet, NC), a zinc deficient diet ad libitum (8 μg zinc/g diet, ZnD). Pup rats were served as experimental subjects. From day 1 of pregnancy upon delivery, maternal rats were given a standard diet (30 mg/kg/day zinc) or zinc deficient diet (8 mg/kg/day zinc) respectively. Adult male 10-week Wistar rats were divided into two dietary groups for 17 weeks of feeding: a control diet ad libitum (30 μg zinc/g diet, NC), a zinc deficient diet ad libitum (8 μg zinc/g diet, ZnD). The birth time of newborn pups was recorded as the zero week. For adult male rats, the time of receiving different assigned diet was recorded as the zeroth week. Newborn pups of these maternal rats were immunized with BCG vaccine or MTB antigen ESAT-6/CFP-10 at postnatal 0 and 2 week. The adult male rats were immunized on the 12th and 14th week. Then, blood samples, thymus and spleen from the rats were harvested for detection of humoral and cell-mediated immune responses using ELISA, MTT and QRT-PCR analysis. Decreased INF-γ and TNF-α production in plasma, changes of expression level of ZIP2, ZIP8, NF-κB and IL-6 mRNA in immune organs, together with reduced T cell proliferation was observed in pups and adult BCG rats suffered from dietary zinc deficiency. Small differences were observed between rats received BCG vaccine and MTB antigen ESAT-6/CFP-10. RESULTS Our data clearly indicate that dietary zinc deficiency can weaken the plasma cytokine levels and cell-mediated responses to BCG and ESAT-6/CFP-10 vaccine via decreasing T cell proliferation, down-regulating INF-γ and TNF-α production and affecting the expression of ZIP2, ZIP8, NF-κB and IL-6 mRNA. In addition, the vaccine immunogenicity of BCG and ESAT-6/CFP-10 was not significantly affected by the time of vaccination.
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Affiliation(s)
- Lina Shi
- Departmnet of Biochemistry and Molecular Biology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong 250012, China
| | - Lianying Zhang
- Departmnet of Biochemistry and Molecular Biology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong 250012, China.
| | - Changcai Li
- Departmnet of Biochemistry and Molecular Biology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong 250012, China
| | - Xiaoyan Hu
- Departmnet of Biochemistry and Molecular Biology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong 250012, China
| | - Xiaolei Wang
- Shandong Provincial Chest Hospital, Jinan, Shandong, China
| | - Qing Huang
- Shandong Provincial Chest Hospital, Jinan, Shandong, China
| | - Gengyin Zhou
- Departmnet of Pathology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong 250012, China
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31
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Tsave O, Halevas E, Yavropoulou MP, Kosmidis Papadimitriou A, Yovos JG, Hatzidimitriou A, Gabriel C, Psycharis V, Salifoglou A. Structure-specific adipogenic capacity of novel, well-defined ternary Zn(II)-Schiff base materials. Biomolecular correlations in zinc-induced differentiation of 3T3-L1 pre-adipocytes to adipocytes. J Inorg Biochem 2015; 152:123-37. [PMID: 26383120 DOI: 10.1016/j.jinorgbio.2015.08.014] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2015] [Revised: 08/02/2015] [Accepted: 08/05/2015] [Indexed: 10/23/2022]
Abstract
Among the various roles of zinc discovered to date, its exogenous activity as an insulin mimetic agent stands as a contemporary challenge currently under investigation and a goal to pursue in the form of a metallodrug against type 2 Diabetes Mellitus. Poised to investigate the adipogenic potential of Zn(II) and appropriately configure its coordination sphere into well-defined anti-diabetic forms, (a) a series of new well-defined ternary dinuclear Zn(II)-L (L=Schiff base ligands with a variable number of alcoholic moieties) compounds were synthesized and physicochemically characterized, (b) their cytotoxicity and migration effect(s) in both pre- and mature adipocytes were assessed, (c) their ability to effectively induce cell differentiation of 3T3-L1 pre-adipocytes into mature adipocytes was established, and (d) closely linked molecular targets involving or influenced by the specific Zn(II) forms were perused through molecular biological techniques, cumulatively delineating factors involved in Zn(II)-induced adipogenesis. Collectively, the results (a) reveal the significance of key structural features of Schiff ligands coordinated to Zn(II), thereby influencing its (a)toxicity behavior and insulin-like activity, (b) project molecular targets influenced by the specific forms of Zn(II) formulating its adipogenic potential, and (c) exemplify the interwoven relationship between Zn(II)-L structural speciation and insulin mimetic biological activity, thereby suggesting ways of fine tuning structure-specific zinc-induced adipogenicity in future efficient antidiabetic drugs.
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Affiliation(s)
- O Tsave
- Laboratory of Inorganic Chemistry, Department of Chemical Engineering, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece
| | - E Halevas
- Laboratory of Inorganic Chemistry, Department of Chemical Engineering, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece
| | - M P Yavropoulou
- Laboratory of Clinical and Molecular Endocrinology, 1st Department of Internal Medicine, AHEPA, University Hospital, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece
| | - A Kosmidis Papadimitriou
- Laboratory of Inorganic Chemistry, Department of Chemical Engineering, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece
| | - J G Yovos
- Laboratory of Clinical and Molecular Endocrinology, 1st Department of Internal Medicine, AHEPA, University Hospital, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece
| | - A Hatzidimitriou
- Laboratory of Inorganic Chemistry, Department of Chemistry, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece
| | - C Gabriel
- Laboratory of Inorganic Chemistry, Department of Chemical Engineering, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece; Center for Research of the Structure of Matter, Magnetic Resonance Laboratory, Department of Chemical Engineering, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece
| | - V Psycharis
- Institute of Advanced Materials, Physicochemical Processes, Nanotechnology and Microsystems, Department of Materials Science, N.C.S.R. "Demokritos", Aghia Paraskevi 15310, Attiki, Greece
| | - A Salifoglou
- Laboratory of Inorganic Chemistry, Department of Chemical Engineering, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece.
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Alterations in zinc binding capacity, free zinc levels and total serum zinc in a porcine model of sepsis. Biometals 2015; 28:693-700. [PMID: 25940830 DOI: 10.1007/s10534-015-9858-4] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2015] [Accepted: 04/24/2015] [Indexed: 01/24/2023]
Abstract
Zinc is crucial for immune function. In addition, the redistribution of zinc and other nutrients due to infection is an integral part of the host immune response to limit availability to pathogens. However, the major zinc binding protein albumin is down regulated during the acute phase response, implicating a decrease in zinc binding capacity. A prospective animal study with eight female German landrace pigs was conducted to investigate alterations in zinc binding capacity, total serum zinc and free zinc levels in the initial phase of sepsis. Sepsis was induced by instillation of autologous feces via midline laparotomy. Total serum zinc declined significantly after 1 h (10.89 ± 0.42 µM vs. 7.67 ± 0.41 µM, p < 0.001), total serum copper and iron reached a significant reduction at 4 h. Urinary excretion of zinc declined in line with total serum zinc. In comparison to total serum zinc, free zinc levels declined to a lesser, though significant, extent. Zinc binding capacity of serum decreased over time, whereby free zinc levels after addition of zinc correlated negatively with total serum protein and albumin levels. In addition IL-6 and TNF-α concentrations were measured and increased significantly 2 h after induction of sepsis. Hence, total serum zinc was the first marker of inflammation in our experiment, and might therefore be a promising biomarker for the early diagnosis of sepsis. Furthermore the observation of a substantially different serum free zinc homeostasis during sepsis provides valuable information for a potential therapeutic zinc supplementation, which has to take buffering capacity by serum proteins into account.
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Samaddar P, Sen K. Species dependent sustainable preconcentration of zinc: Possible aspects of ABS and CPE. J IND ENG CHEM 2015. [DOI: 10.1016/j.jiec.2014.04.020] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
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Skrovanek S, DiGuilio K, Bailey R, Huntington W, Urbas R, Mayilvaganan B, Mercogliano G, Mullin JM. Zinc and gastrointestinal disease. World J Gastrointest Pathophysiol 2014; 5:496-513. [PMID: 25400994 PMCID: PMC4231515 DOI: 10.4291/wjgp.v5.i4.496] [Citation(s) in RCA: 90] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2014] [Revised: 09/18/2014] [Accepted: 10/01/2014] [Indexed: 02/06/2023] Open
Abstract
This review is a current summary of the role that both zinc deficiency and zinc supplementation can play in the etiology and therapy of a wide range of gastrointestinal diseases. The recent literature describing zinc action on gastrointestinal epithelial tight junctions and epithelial barrier function is described. Zinc enhancement of gastrointestinal epithelial barrier function may figure prominently in its potential therapeutic action in several gastrointestinal diseases.
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Barnable P, Calenda G, Ouattara L, Gettie A, Blanchard J, Jean-Pierre N, Kizima L, Rodríguez A, Abraham C, Menon R, Seidor S, Cooney ML, Roberts KD, Sperling R, Piatak M, Lifson JD, Fernandez-Romero JA, Zydowsky TM, Robbiani M, Teleshova N. A MIV-150/zinc acetate gel inhibits SHIV-RT infection in macaque vaginal explants. PLoS One 2014; 9:e108109. [PMID: 25259616 PMCID: PMC4178065 DOI: 10.1371/journal.pone.0108109] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2014] [Accepted: 08/19/2014] [Indexed: 11/19/2022] Open
Abstract
To extend our observations that single or repeated application of a gel containing the NNRTI MIV-150 (M) and zinc acetate dihydrate (ZA) in carrageenan (CG) (MZC) inhibits vaginal transmission of simian/human immunodeficiency virus (SHIV)-RT in macaques, we evaluated safety and anti-SHIV-RT activity of MZC and related gel formulations ex vivo in macaque mucosal explants. In addition, safety was further evaluated in human ectocervical explants. The gels did not induce mucosal toxicity. A single ex vivo exposure to diluted MZC (1∶30, 1∶100) and MC (1∶30, the only dilution tested), but not to ZC gel, up to 4 days prior to viral challenge, significantly inhibited SHIV-RT infection in macaque vaginal mucosa. MZC's activity was not affected by seminal plasma. The antiviral activity of unformulated MIV-150 was not enhanced in the presence of ZA, suggesting that the antiviral activity of MZC was mediated predominantly by MIV-150. In vivo administration of MZC and CG significantly inhibited ex vivo SHIV-RT infection (51-62% inhibition relative to baselines) of vaginal (but not cervical) mucosa collected 24 h post last gel exposure, indicating barrier effect of CG. Although the inhibitory effect of MZC (65-74%) did not significantly differ from CG (32-45%), it was within the range of protection (∼75%) against vaginal SHIV-RT challenge 24 h after gel dosing. Overall, the data suggest that evaluation of candidate microbicides in macaque explants can inform macaque efficacy and clinical studies design. The data support advancing MZC gel for clinical evaluation.
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Affiliation(s)
- Patrick Barnable
- Population Council, New York, New York, United States of America
| | - Giulia Calenda
- Population Council, New York, New York, United States of America
| | - Louise Ouattara
- Population Council, New York, New York, United States of America
| | - Agegnehu Gettie
- Aaron Diamond AIDS Research Center, Rockefeller University, New York, New York, United States of America
| | - James Blanchard
- Tulane National Primate Research Center, Tulane University, Covington, Louisiana, United States of America
| | | | - Larisa Kizima
- Population Council, New York, New York, United States of America
| | - Aixa Rodríguez
- Population Council, New York, New York, United States of America
| | - Ciby Abraham
- Population Council, New York, New York, United States of America
| | - Radhika Menon
- Population Council, New York, New York, United States of America
| | - Samantha Seidor
- Population Council, New York, New York, United States of America
| | | | - Kevin D. Roberts
- Population Council, New York, New York, United States of America
| | - Rhoda Sperling
- Icahn School of Medicine at Mount Sinai, New York, New York, United States of America
| | - Michael Piatak
- AIDS and Cancer Virus Program, SAIC-Frederick, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, United States of America
| | - Jeffrey D. Lifson
- AIDS and Cancer Virus Program, SAIC-Frederick, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, United States of America
| | | | | | - Melissa Robbiani
- Population Council, New York, New York, United States of America
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Schubert C, Guttek K, Grüngreiff K, Thielitz A, Bühling F, Reinhold A, Brocke S, Reinhold D. Oral zinc aspartate treats experimental autoimmune encephalomyelitis. Biometals 2014; 27:1249-62. [DOI: 10.1007/s10534-014-9786-8] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2014] [Accepted: 08/13/2014] [Indexed: 01/17/2023]
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37
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Elahi A, Singh M, Ali S, Khan F. Antigen specific immune enhancement of innate and acquired immunity by pearl in ashed form. Int Immunopharmacol 2014; 21:82-93. [DOI: 10.1016/j.intimp.2014.04.013] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2013] [Revised: 03/24/2014] [Accepted: 04/13/2014] [Indexed: 11/26/2022]
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Abstract
Even though zinc is essential for virtually all processes in the human body, observations during zinc deficiency indicate that the absence of this trace element most severely affects the immune response. Numerous investigations of the cellular and molecular requirements for zinc in the immune system have indicated that there is not just one single function of zinc underlying this essentiality. In fact, there is a wide range of different roles of zinc in immunity. This review summarizes the recent developments in three of the major fields: the role of zinc as a second messenger in signal transduction, the importance of zinc for immune cell function, and the competition for zinc between the host and the pathogen, a concept known as nutritional immunity.
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Affiliation(s)
- Hajo Haase
- Institute of Immunology, Medical Faculty, RWTH Aachen University, Pauwelsstrasse 30, 52074 Aachen, Germany.
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Kaur K, Gupta R, Saraf SA, Saraf SK. Zinc: The Metal of Life. Compr Rev Food Sci Food Saf 2014; 13:358-376. [PMID: 33412710 DOI: 10.1111/1541-4337.12067] [Citation(s) in RCA: 90] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2013] [Accepted: 02/05/2014] [Indexed: 01/15/2023]
Abstract
The importance of zinc was 1st reported for Aspergillus niger. It took over 75 y to realize that zinc is also an essential trace element for rats, and an additional 30 y went by before it was recognized that this was also true for humans. The adult body contains about 2 to 3 g of zinc. Zinc is found in organs, tissues, bones, fluids, and cells. It is essential for many physiological functions and plays a significant role in a number of enzyme actions in the living systems. Bioinformatics estimates report that 10% of the human proteome contains zinc-binding sites. Based on its role in such a plethora of cellular components, zinc has diverse biological functions from enzymatic catalysis to playing a crucial role in cellular neuronal systems. Thus, based on the various published studies and reports, it is pertinent to state that zinc is one of the most important essential trace metals in human nutrition and lifestyle. Its deficiency may severely affect the homeostasis of a biological system. This review compiles the role of zinc in prophylaxis/therapeutics and provides current information about its effect on living beings.
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Affiliation(s)
- Kuljeet Kaur
- Faculty of Pharmacy, Babu Banarasi Das Natl. Inst. of Technology and Management (BBD Univ.), Lucknow, India
| | - Rajiv Gupta
- Faculty of Pharmacy, Babu Banarasi Das Natl. Inst. of Technology and Management (BBD Univ.), Lucknow, India
| | - Shubhini A Saraf
- Dept. of Pharmaceutical Sciences, SB&BT, Babasaheb Bhimrao Ambedkar Univ., Lucknow, India
| | - Shailendra K Saraf
- Faculty of Pharmacy, Babu Banarasi Das Northern India Inst. of Technology, Lucknow, India
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40
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Harmaza YM, Slobozhanina EI. Zinc essentiality and toxicity. Biophysical aspects. Biophysics (Nagoya-shi) 2014. [DOI: 10.1134/s0006350914020092] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
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Wang X, Li X, Onuma K, Sogo Y, Ohno T, Ito A. Zn- and Mg- containing tricalcium phosphates-based adjuvants for cancer immunotherapy. Sci Rep 2014; 3:2203. [PMID: 23857555 PMCID: PMC3712317 DOI: 10.1038/srep02203] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2013] [Accepted: 06/27/2013] [Indexed: 12/24/2022] Open
Abstract
Zn-, and Mg-containing tricalcium phosphates (TCPs) loaded with a hydrothermal extract of a human tubercle bacillus (HTB) were prepared by immersing Zn-TCP and Mg-TCP in HTB-containing supersaturated calcium phosphate solutions. The in vitro and in vivo immunogenic activities of the HTB-loaded Zn-, and Mg-TCPs (Zn-Ap-HTB and Mg-Ap-HTB, respectively) were evaluated as potential immunopotentiating adjuvants for cancer immunotherapy. The Zn-Ap-HTB and Mg-Ap-HTB adjuvants showed no obvious cytotoxicity and more effectively stimulated granulocyte-macrophage colony-stimulating factor (GM-CSF) secretion by macrophage-like cells than unprocessed HTB or HTB-loaded TCP (T-Ap-HTB) in vitro. Zn-Ap-HTB and Mg-Ap-HTB mixed with liquid-nitrogen-treated tumor tissue markedly inhibited the in vivo development of rechallenged Lewis lung carcinoma (LLC) cells compared with T-Ap-HTB and the unprocessed HTB mixed liquid-nitrogen-treated tumor tissue. Zn-Ap-HTB and Mg-Ap-HTB contributed to eliciting potent systemic antitumor immunity in vivo.
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Affiliation(s)
- Xiupeng Wang
- Human Technology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki, Japan.
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42
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Haase H, Rink L. Zinc signals and immune function. Biofactors 2014; 40:27-40. [PMID: 23804522 DOI: 10.1002/biof.1114] [Citation(s) in RCA: 170] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2013] [Revised: 04/23/2013] [Accepted: 04/25/2013] [Indexed: 12/21/2022]
Abstract
For more than 50 years, it has been known that zinc deficiency compromises immune function. During this time, knowledge about the biochemistry of zinc has continued to grow, but only recent years have provided in-depth molecular insights into the multiple aspects of zinc as a regulator of immunity. A network based on ZnT and ZIP proteins for transport and metallothionein for storage tightly regulates zinc availability, and virtually all aspects of innate and adaptive immunity are affected by zinc. In vivo, zinc deficiency alters the number and function of neutrophil granulocytes, monocytes, natural killer (NK)-, T-, and B-cells. T cell functions and balance between the different subsets are particularly susceptible to changes in zinc status. This article focuses in particular on the main mechanisms by which zinc ions exert essential functions in the immune system. On the one hand, this includes tightly protein bound zinc ions serving catalytic or structural functions in a multitude of different proteins, in particular enzymes and transcription factors. On the other hand, increasing evidence arises for a regulatory role of free zinc ions in signal transduction, especially in cells of the immune system. Identification of several molecular targets, including phosphatases, phosphodiesterases, caspases, and kinases suggest that zinc ions are a second messenger regulating signal transduction in various kinds of immune cells.
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Affiliation(s)
- Hajo Haase
- Institute of Immunology, Medical Faculty, RWTH Aachen University, Pauwelsstrasse 30, Aachen, Germany
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43
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Mao L, Chen J, Peng Q, Zhou A, Wang Z. Effects of different sources and levels of zinc on H2O2-induced apoptosis in IEC-6 cells. Biol Trace Elem Res 2013; 155:132-41. [PMID: 23912254 DOI: 10.1007/s12011-013-9759-8] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2013] [Accepted: 07/09/2013] [Indexed: 12/14/2022]
Abstract
Zinc has been shown to be an inhibitor of apoptosis for many years. The present study was designed to investigate effects of three zinc chemical forms on H2O2-induced cell apoptosis in IEC-6 cells via analysis of cell vitality, LDH activity, apoptosis percentage, caspase-3 activity, and Bcl-2, Bax, and caspase-3, -8, and -9 gene expression. Cells were divided into H2O2 and zinc sources+H2O2 groups, and there are three different zinc sources [zinc oxide nanoparticle (nano-ZnO), zinc oxide (ZnO), and zinc sulfate (ZnSO4)] and three concentrations (normal = 25 μM, medium = 50 μM, and high = 100 μM) used in this article. In the present study, we found the striking cytotoxicity of H2O2 higher than 200 μM on cell vitality, LDH activity, and apoptosis percentage in the cells using five different concentrations (50, 100, 200, 400, and 800 μM) of H2O2 for 4 h. Moreover, we observed that cell vitality was increased, LDH activity and apoptotic percentage were decreased, and gene expression level of Bax and caspase-3 and -9 was markedly reduced, while gene expression level of Bcl-2 and ratio of Bcl-2/Bax were increased in normal concentration groups of nano-ZnO and ZnSO4 compared with H2O2 group, but no significant difference was observed in caspase-8 gene expression. Furthermore, medium or, more intensely, high concentrations of nano-ZnO and ZnSO4 enhanced H2O2-induced cell apoptosis. Compared with nano-ZnO and ZnSO4, ZnO showed weakest protective effect on H2O2-induced apoptosis at normal concentration and was less toxic to cells at high level. Taken together, we proposed that preventive and protective effects of zinc on H2O2-induced cell apoptosis varied in IEC-6 cells with its chemical forms and concentrations, and maybe for the first time, we suggested that nano-ZnO have a protective effect on H2O2-induced cell apoptosis in IEC-6 cells.
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Affiliation(s)
- Lei Mao
- Institute of Animal Nutrition, Key Laboratory of Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Ya' an, People's Republic of China
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Wang TH, Jian CH, Hsieh YK, Wang FN, Wang CF. Spatial distributions of inorganic elements in honeybees (Apis mellifera L.) and possible relationships to dietary habits and surrounding environmental pollutants. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2013; 61:5009-5015. [PMID: 23646931 DOI: 10.1021/jf400695w] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/02/2023]
Abstract
In this study, the laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) was adopted to determine the distribution of inorganic elements, including Ca, Cu, Fe, Mg, Mn, S, P, Pb, and Zn, in honeybees (Apis melifera L.). Two features are particularly noteworthy. First, it was found there is a significant amount of Fe located at the fringe of the abdomen in worker bees; ultrasonic imaging, scanning electron microscopy, and magnetic resonance imaging revealed that it arose from magnetic Fe-bearing nanoparticles (NPs) having an average diameter of approximately 40 nm. Interestingly, only worker bees contained these magnetic Fe-bearing NPs; no similar features appeared in larvae, pupae, wasps, or drones. Second, a detectable amount of Pb accumulated particularly in the alimentary canals of worker bees. Again, no detectable amounts of Pb in larvae, pupae, drones, or wasps, yet a level of 0.24 ± 0.05 mg/kg of Pb in pollen; therefore, the diet appears to be the primary pathway for environmental pollutants entering the honeybees' food chain.
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Affiliation(s)
- Tsing-Hai Wang
- Biomedical Engineering and Environment Sciences, National Tsing Hua University, Taiwan
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Up-regulation of Slc39A2(Zip2) mRNA in peripheral blood mononuclear cells from patients with pulmonary tuberculosis. Mol Biol Rep 2013; 40:4979-84. [PMID: 23686108 DOI: 10.1007/s11033-013-2598-z] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2012] [Accepted: 04/29/2013] [Indexed: 01/26/2023]
Abstract
Zinc is the most common trace mineral after iron in the human body. In organisms, zinc transporters help zinc influx and efflux from cells. A previous study has reported that Zip2 was up-regulated over 27-fold in human monocytic THP-1 cells, when intracellular zinc was depleted by TPEN. Our study found Zip2 was over-expressed in leukocytes of asthmatic infants, especially those in which the serum zinc level was lower than those in healthy infants. Pulmonary tuberculosis (PTB) patients have significantly low serum zinc levels. Here we investigated whether Zip2 level was changed in the patients with PTB. Zip2 mRNA and protein levels in peripheral blood mononuclear cells (PBMC) from PTB (n1=23) and healthy controls (n2=42) were detected by quantitative real-time PCR and western blot, respectively. mRNA expression levels of another four zinc transporters, Zip1, Zip6, Zip8 and ZnT1, were detected by quantitative real-time PCR. Zip2 mRNA level was significantly up-regulated in PTB patients (P=0.001), and Zip8 mRNA level was significantly down-regulated compared with control individuals (P<0.001). In contrast, there were no significant changes in mRNA levels of Zip1, Zip6 and ZnT1 in either group (P>0.05). Zip2 protein expression levels increased in PTB patients compared with control individuals. Our study found that knockdown of ZIP2 with siRNA caused a decrease in Zip2 levels in PBMC of PTB patients, while reducing the expression of INF-γ (P<0.01) and increasing the expression of IL-6(P<0.01). These data provide evidence that increased expression of Zip2 gene is closely associated with immunity of PTB patients, suggesting that the Zip2 gene may play a key role in the initial infection control of the human body, by promoting and maintaining the immune response of adaptive T cells.
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Hong SH, Choi YS, Cho HJ, Lee JY, Hwang TK, Kim SW. Induction of apoptosis of bladder cancer cells by zinc-citrate compound. Korean J Urol 2012. [PMID: 23185674 PMCID: PMC3502741 DOI: 10.4111/kju.2012.53.11.800] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Abstract
Purpose Zinc is one of the trace minerals in the body and is known to have an anticancer effect by inducing apoptosis in prostate cancer. We aimed to investigate the antiproliferative effects of a zinc-citrate compound in bladder cancer. Materials and Methods A bladder cancer cell line (MBT-2) was treated with a zinc-citrate compound at different time intervals and concentrations. Mitochondrial (m)-aconitase activity was determined by use of the aconitase assay. DNA laddering analysis was performed to investigate apoptosis of MBT-2 cells. The molecular mechanism of apoptosis was investigated by Western blot analysis of p53, p21waf1, Bcl-2, Bcl-xL, and Bax and also by caspase-3 activity analysis. Results Treatment with the zinc-citrate compound resulted in a time- and dose-dependent decrease in cell number of MBT-2 cells. M-aconitase activity was significantly decreased. DNA laddering analysis indicated apoptosis of MBT-2 cells. The zinc-citrate compound increased the expression of p21waf1 and p53 and reduced the expression of Bcl-2 and Bcl-xL proteins but induced expression of Bax protein. The zinc-citrate compound induced apoptosis of MBT-2 cells by activation of the caspase-3 pathway. Conclusions We have shown that a zinc-citrate compound induces apoptotic cell death in a bladder cancer cell line, MBT-2, by caspase-3 activation through up-regulation of apoptotic proteins and down-regulation of antiapoptotic proteins.
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Affiliation(s)
- Sung-Hoo Hong
- Department of Urology, The Catholic University of Korea College of Medicine, Seoul, Korea
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Hasan R, Rink L, Haase H. Zinc signals in neutrophil granulocytes are required for the formation of neutrophil extracellular traps. Innate Immun 2012; 19:253-64. [DOI: 10.1177/1753425912458815] [Citation(s) in RCA: 69] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023] Open
Abstract
Zinc signals, i.e. changes in the free intracellular Zn2+concentration, are an integral component of signal transduction in several immune cells. The aim of the present study was to investigate if this is also the case in neutrophil granulocytes. One neutrophil function is NETosis, the release of a matrix composed of DNA, chromatin and granule proteins to capture extracellular bacteria within so-called neutrophil extracellular traps (NET). NETosis can be induced by the protein kinase C (PKC) activator 12-myristate 13-acetate (PMA). PMA treatment led to a zinc signal in neutrophil granulocytes. NETosis was inhibited when the zinc signal was sequestered by the membrane permeable high affinity chelator N, N, N′, N′,-tetrakis (2-pyridylmethyl)ethylenediamine (TPEN). PKC-mediated NET formation depends on the production of reactive oxygen species (ROS) by NADPH oxidase. Inhibition of NADPH oxidase with diphenyleneiodonium chloride blocked ROS formation and NETosis, as well as the zinc signal. TPEN, however, had no effect on PKC activity and ROS production, indicating that Zn2+ is not required for activation of PKC, but for signals downstream of ROS production. In conclusion, zinc signals are an essential component of the ROS-dependent signal transduction leading to NETosis.
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Affiliation(s)
- Rafah Hasan
- RWTH Aachen University Hospital, Medical Faculty, Institute of Immunology, Germany
| | - Lothar Rink
- RWTH Aachen University Hospital, Medical Faculty, Institute of Immunology, Germany
| | - Hajo Haase
- RWTH Aachen University Hospital, Medical Faculty, Institute of Immunology, Germany
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Daaboul D, Rosenkranz E, Uciechowski P, Rink L. Repletion of zinc in zinc-deficient cells strongly up-regulates IL-1β-induced IL-2 production in T-cells. Metallomics 2012; 4:1088-97. [PMID: 22983538 DOI: 10.1039/c2mt20118f] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Mild zinc deficiency in humans negatively affects IL-2 production resulting in declined percentages of cytolytic T cells and decreased NK cell lytic activity, which enhances the susceptibility to infections and malignancies. T-cell activation is critically regulated by zinc and the normal physiological zinc level in T-cells slightly lies below the optimal concentration for T-cell functions. A further reduction in zinc level leads to T-cell dysfunction and autoreactivity, whereas high zinc concentrations (100 μM) were shown to inhibit interleukin-1 (IL-1)-induced IL-1 receptor kinase (IRAK) activation. In this study, we investigated the molecular mechanism by which zinc regulates the IL-1β-induced IL-2 expression in T-cells. Zinc supplementation to zinc-deficient T-cells increased intracellular zinc levels by altering the expression of zinc transporters, particularly Zip10 and Zip12. A zinc signal was observed in the murine T-cell line EL-4 6.1 after 1 h of stimulation with IL-1β, measured by specific zinc sensors FluoZin-3 and ZinPyr-1. This signal is required for the phosphorylation of MAPK p38 and NF-κB subunit p65, which triggers the transcription of IL-2 and strongly increases its production. These results indicate that short-term zinc supplementation to zinc-deficient T-cells leads to a fast rise in zinc levels which subsequently enhance cytokine production. In conclusion, low and excessive zinc levels might be equally problematic for zinc-deficient subjects, and stabilized zinc levels seem to be essential to avoid negative concentration-dependent zinc effects on T-cell activation.
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Affiliation(s)
- Doha Daaboul
- Institute of Immunology, RWTH Aachen University Hospital, Medical Faculty, Pauwelsstrasse 30, D-52074 Aachen, Germany
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Zinc and regulation of inflammatory cytokines: implications for cardiometabolic disease. Nutrients 2012; 4:676-94. [PMID: 22852057 PMCID: PMC3407988 DOI: 10.3390/nu4070676] [Citation(s) in RCA: 177] [Impact Index Per Article: 13.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2012] [Revised: 06/08/2012] [Accepted: 06/25/2012] [Indexed: 12/17/2022] Open
Abstract
In atherosclerosis and diabetes mellitus, the concomitant presence of low-grade systemic inflammation and mild zinc deficiency highlights a role for zinc nutrition in the management of chronic disease. This review aims to evaluate the literature that reports on the interactions of zinc and cytokines. In humans, inflammatory cytokines have been shown both to up- and down-regulate the expression of specific cellular zinc transporters in response to an increased demand for zinc in inflammatory conditions. The acute phase response includes a rapid decline in the plasma zinc concentration as a result of the redistribution of zinc into cellular compartments. Zinc deficiency influences the generation of cytokines, including IL-1β, IL-2, IL-6, and TNF-α, and in response to zinc supplementation plasma cytokines exhibit a dose-dependent response. The mechanism of action may reflect the ability of zinc to either induce or inhibit the activation of NF-κB. Confounders in understanding the zinc-cytokine relationship on the basis of in vitro experimentation include methodological issues such as the cell type and the means of activating cells in culture. Impaired zinc homeostasis and chronic inflammation feature prominently in a number of cardiometabolic diseases. Given the high prevalence of zinc deficiency and chronic disease globally, the interplay of zinc and inflammation warrants further examination.
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Sankavaram K, Freake HC. The effects of transformation and ZnT-1 silencing on zinc homeostasis in cultured cells. J Nutr Biochem 2012; 23:629-34. [DOI: 10.1016/j.jnutbio.2011.03.006] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2010] [Revised: 09/21/2010] [Accepted: 03/03/2011] [Indexed: 01/08/2023]
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