Prospective Cohort Study

Advances in metal-induced oxidative stress and human disease

Objective:To assess the magnitude and direction of associations of depression with C-reactive protein (CRP), interleukin (IL)-1, and IL-6 in community and clinical samples.Methods:Systematic review of articles published between January 1967 and January 2008 in the PubMed and PsycINFO electronic data

Associations of Depression With C-Reactive Protein, IL-1, and IL-6 : A Meta-Analysis

This article reviews the literature regarding the structure and function of two types of exotoxins expressed by Staphylococcus aureus, pyrogenic toxin superantigens (PTSAgs) and hemolysins. The molecular basis of PTSAg toxicity is presented in the context of two diseases known to be caused by these exotoxins: toxic shock syndrome and staphylococcal food poisoning. The family of staphylococcal PTSAgs presently includes toxic shock syndrome toxin-1 (TSST-1) and most of the staphylococcal enterotoxins (SEs) (SEA, SEB, SEC, SED, SEE, SEG, and SEH). As the name implies, the PTSAgs are multifunctional proteins that invariably exhibit lethal activity, pyrogenicity, superantigenicity, and the capacity to induce lethal hypersensitivity to endotoxin. Other properties exhibited by one or more staphylococcal PTSAgs include emetic activity (SEs) and penetration across mucosal barriers (TSST-1). A detailed review of the molecular mechanisms underlying the toxicity of the staphylococcal hemolysins is also presented.

Exotoxins of Staphylococcus aureus

The recent sequencing of the entire genomes of Mycoplasma genitalium and M. pneumoniae has attracted considerable attention to the molecular biology of mycoplasmas, the smallest self-replicating organisms. It appears that we are now much closer to the goal of defining, in molecular terms, the entire machinery of a self-replicating cell. Comparative genomics based on comparison of the genomic makeup of mycoplasmal genomes with those of other bacteria, has opened new ways of looking at the evolutionary history of the mycoplasmas. There is now solid genetic support for the hypothesis that mycoplasmas have evolved as a branch of gram-positive bacteria by a process of reductive evolution. During this process, the mycoplasmas lost considerable portions of their ancestors’ chromosomes but retained the genes essential for life. Thus, the mycoplasmal genomes carry a high percentage of conserved genes, greatly facilitating gene annotation. The significant genome compaction that occurred in mycoplasmas was made possible by adopting a parasitic mode of life. The supply of nutrients from their hosts apparently enabled mycoplasmas to lose, during evolution, the genes for many assimilative processes. During their evolution and adaptation to a parasitic mode of life, the mycoplasmas have developed various genetic systems providing a highly plastic set of variable surface proteins to evade the host immune system. The uniqueness of the mycoplasmal systems is manifested by the presence of highly mutable modules combined with an ability to expand the antigenic repertoire by generating structural alternatives, all compressed into limited genomic sequences. In the absence of a cell wall and a periplasmic space, the majority of surface variable antigens in mycoplasmas are lipoproteins. Apart from providing specific antimycoplasmal defense, the host immune system is also involved in the development of pathogenic lesions and exacerbation of mycoplasma induced diseases. Mycoplasmas are able to stimulate as well as suppress lymphocytes in a nonspecific, polyclonal manner, both in vitro and in vivo. As well as to affecting various subsets of lymphocytes, mycoplasmas and mycoplasma-derived cell components modulate the activities of monocytes/macrophages and NK cells and trigger the production of a wide variety of up-regulating and down-regulating cytokines and chemokines. Mycoplasma-mediated secretion of proinflammatory cytokines, such as tumor necrosis factor alpha, interleukin-1 (IL-1), and IL-6, by macrophages and of up-regulating cytokines by mitogenically stimulated lymphocytes plays a major role in mycoplasma-induced immune system modulation and inflammatory responses.

Molecular Biology and Pathogenicity of Mycoplasmas

In renal transplantation, rejection of the allograft is still a problem despite of new immunosuppressive strategies and improved HLA-matching by molecular typing methods. Survival of the graft mainly depends on the number of HLA-mismatches between donor and recipient. However, case reports revealed that even full matched cadaveric organs may undergo repeated rejection episodes resulting in the loss of the renal graft. Several mechanisms may be responsible for this poorly understood event. The alloreactivity may possibly be induced by HLA-subtypes not being characterised until now, silent HLA-mismatches or proteins of human endogenous retroviruses (HERV) which correspond to the minor lymphocyte stimulating antigens (Mis) in the mouse [1]. These Mis were first described in mixed lymphocyte culture experiments (MLC) of MHC-identical mouse strains while stimulating lymphocytes despite MHC-identity. Since perfectly HLA-matched donors were only found in very few cases [2] the problem of acceptable and non-acceptable mismatches between donor and recipient is even more obvious in transplantation medicine. Little is known on how to identify these combinations. A useful test should directly quantify the activation of T-helper-cell- (TH-) subpopulations of donor and recipient and therefore measure the biological relevance of stimulating antigens. The functional in vitro T-cell assays are used for this purpose, especially MLC. Recently, it is discussed whether measurement of cytokines in the two-way MLC may probably be used for the prediction of the rejection or the acceptance of a graft. The conventional standard oneway MLC test measures the cell proliferation between antigen-presenting cells (APC) and T-cells of host and graft and vice versa. It has been established in the clinical routine of bone marrow transplantation (BMT) for many years. However, the measurement of the proliferation in one-way MLC has no satisfying predictive value for the outcome of transplantation of either bone marrow or renal allografts [3].

Reverse transcription polymerase chain reaction for cytokines in the mixed lymphocyte culture. Is there a role in renal transplantation

(1) Background: Zinc is suggested to play a major role in epidermal growth factor (EGF)-induced cell regeneration and proliferation. To deepen the knowledge on the underlying mechanisms zinc's effects on the epidermal growth factor receptor (EGFR) activation and its endocytosis was investigated in the alveolar carcinoma cell line A549. (2) Methods: An increase of intracellular zinc was generated by adding zinc extracellularly compared to the intracellular release of zinc from zinc-binding proteins by stimulation with a nitric oxide donor. Zinc-initiated EGFR phosphorylation was checked by Western blotting and receptor endocytosis assays were performed by using flow cytometry. (3) Results: Besides a dose-dependent EGFR phosphorylation, a dose- and time dependent significant receptor internalisation was initiated by both types of zinc increases. In addition, both increased intracellular zinc levels further promoted EGF-induced EGFR phosphorylation and internalisation. (4) Conclusion: This report confirms a transactivating effect of zinc on the EGFR for A549 cells and is the first describing an influence of zinc on the EGFR endocytosis. The transferability of the fine-tuning of EGFR-induced signalling by zinc needs to be verified in vivo, but the presented data underline that zinc might be helpful during treatment of disturbed regeneration and tissue repair.

https://www.mdpi.com/1422-0067/22/1/326/pdf

Increase of the Intracellular Zinc Concentration Leads to an Activation and Internalisation of the Epidermal Growth Factor Receptor in A549 Cells.

Zinc and ageing.

SCOPE
T cell activation requires a metabolic reprogramming from oxidative phosphorylation to aerobic glycolysis to rapidly provide substrates for biosynthesis. An individual's zinc status plays an important role in balancing the activation of T cells and is required for a proper function of immune cells. Furthermore, zinc plays an important role during effector T cell polarization to T helper cell subsets or regulatory T cells, with effector T cells relying on glycolysis and regulatory T cells on oxidative phosphorylation. Therefore, we aimed to analyze if zinc also impacts on T cell activation on the level of intracellular metabolism.


METHODS AND RESULTS
We used mixed lymphocyte culture and anti-CD3/CD28 stimulation as in vitro models for T cell activation to investigate the effect of zinc supplementation and deprivation on metabolic switching. We observed promoted glucose uptake, insulin receptor expression and signaling in both zinc conditions, whereas key metabolic enzymes were stimulated mainly by zinc deprivation. Alterations in cytokine production suggest an immune-activating effect of zinc deprivation and a balancing effect of zinc supplementation.


CONCLUSION
Our results suggest a supportive effect of both zinc supplementation and deprivation on the metabolic switch during T cell activation, adding another level of immune regulation by zinc. This article is protected by copyright. All rights reserved.

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/mnfr.202100944

Lothar Rink

Papers

Reverse transcription polymerase chain reaction for cytokines in the mixed lymphocyte culture. Is there a role in renal transplantation

Increase of the Intracellular Zinc Concentration Leads to an Activation and Internalisation of the Epidermal Growth Factor Receptor in A549 Cells.

Zinc and ageing.

Zinc Levels Affect the Metabolic Switch of T Cells by Modulating Glucose Uptake and Insulin Receptor Signaling.

Selection of an inadequate housekeeping gene leads to misinterpretation of target gene expression in zinc deficiency and zinc supplementation models