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

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

Zinc and immune function: the biological basis of altered resistance to infection.

IBD, comprising Crohn's disease and ulcerative colitis, is a chronic immunologically mediated disease at the intersection of complex interactions between genetics, environment and gut microbiota. Established high-prevalence populations of IBD in North America and Europe experienced the steepest increase in incidence towards the second half of the twentieth century. Furthermore, populations previously considered 'low risk' (such as in Japan and India) are witnessing an increase in incidence. Potentially relevant environmental influences span the spectrum of life from mode of childbirth and early-life exposures (including breastfeeding and antibiotic exposure in infancy) to exposures later on in adulthood (including smoking, major life stressors, diet and lifestyle). Data support an association between smoking and Crohn's disease whereas smoking cessation, but not current smoking, is associated with an increased risk of ulcerative colitis. Dietary fibre (particularly fruits and vegetables), saturated fats, depression and impaired sleep, and low vitamin D levels have all been associated with incident IBD. Interventional studies assessing the effects of modifying these risk factors on natural history and patient outcomes are an important unmet need. In this Review, the changing epidemiology of IBD, mechanisms behind various environmental associations and interventional studies to modify risk factors and disease course are discussed.

Epidemiology and risk factors for IBD

Tumor Necrosis Factor α

Implant outcomes in comparison to a natural tooth in a rat model using systemic alendronate and zoledronate acid drug administrations were assessed. Fifty-four Sprague-Dawley rats were randomly allocated into two experimental groups (drug application of zoledronic acid; 0.04 mg/kg intravenously once a week and alendronic acid; 0.2 mg/kg subcutaneously five times a week) and one control group with 18 animals in each group. Drug delivery was conducted for a period of 4 months. After 4 weeks either a zirconia or a titanium implant was immediately inserted in the socket of the first molar of the upper jaw. In vivo investigations included host inflammatory parameters and the implant survival and success rates for up to 3 months. Material incompatibilities against titanium and zirconia nanoparticles were evaluated in vitro after stimulation of rat spleen cells. In vivo, IL-6 release around titanium implants demonstrated significantly higher values in the control group (p = 0.02) when compared to the zoledronic acid group. Around the natural tooth without drug administration, the control group showed higher IL-6 values compared with the alendronic acid group (p = 0.01). In vitro, only lipopolysaccharide and not the implant's nanoparticles stimulated significant IL-6 and TNFα production. In terms of the primary aim of in vivo and in vitro IL-6 and TNFα measurements, no implant material was superior to the other. No significant in vitro stimulation of rat spleen cells was detected with respect to titanium oxide and zirconium oxide nanoparticles. 

https://www.nature.com/articles/s41598-022-08308-8.pdf

Host inflammatory response and clinical parameters around implants in a rat model using systemic alendronate and zoledronate acid drug administrations

Nur durch das Zusammenwirken mehrerer Zelltypen ist eine effektive Immunantwort moglich. Um diese zu koordinieren, gibt es eine Reihe von Mechanismen zur Kommunikation zwischen Immunzellen, unter anderem eine Vielzahl von immunmodulierenden Signalmolekulen, die Cytokine. Cytokine sind Proteine, die von verschiedenen Zellen (d.h. keinen spezialisierten Drusenzellen) produziert werden konnen und uber spezifische Rezeptoren auf der Zellmembran Signale von oder auf Zellen des Immunsystems ubertragen.

Die Regulation des Immunsystems und immunprivilegierte Organe

Zinc Regulation of the Immune Response

SCOPE
Zinc is important for a balanced immune system, but the mechanisms are not yet fully elucidated. One possibility is an interaction of zinc with the tricarbocylic acid cycle (TCA), in which zinc inhibits the mitochondrial aconitase leading to an increase in intracellular citrate concentration as described for prostate cells. Therefore, we studied the immune modulatory effects of zinc and citrate and their interaction in mixed lymphocyte cultures (MLC).


METHODS AND RESULTS
After allogeneic (MLC) or superantigen stimulation, the interferon-γ (IFNγ) production was quantified by ELISA and T cell subpopulations were determined by Western Blot. Intracellular concentrations of citrate and zinc were measured. Zinc and citrate reduce the IFNγ expression and the pro-inflammatory T helper cells (Th) 1 and Th17 in MLC. While zinc increases regulatory T cells, citrate reduces them. After superantigen stimulation IFNγ production is decreased only by citrate but increased by zinc. Zinc does not affect citrate concentration, while citrate impairs zinc uptake. Thus, zinc and citrate independently regulate IFNy expression.


CONCLUSION
These results may explain the immunosuppressive effect of blood products anticoagulated by citrate. In addition, high citrate consumption may lead to immunosuppressive effects, so upper limits for citrate should be established. This article is protected by copyright. All rights reserved.

The influence of zinc and citrate on T cell activation and differentiation in mixed lymphocyte cultures.

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