The Role of the Liver in Iron Homeostasis and What Goes Wrong?

Iron is an essential mineral that is vital for growth development, normal cellular function, synthesis of hormones and connective tissue, and most importantly, serves as a component of hemoglobin to carry oxygen to body tissues. The body finely regulates the amount of circulating and stored iron within the body to maintain concentration levels within range for optimal physiologic function. Without iron, the ability for cells to participate in electron transport and energy metabolism decreases. Furthermore, hemoglobin synthesis is altered, which leads to anemia and decreased oxygen delivery to tissue. Problems arise when there is too little or too much iron. This review explores the role of the liver in iron physiology, iron overload and discusses the most common causes of primary and secondary hepatic iron overload.

Erythropoietin level in normal and abnormal human seminal fluid

Background. There are not enough publications devoted to the study of erythropoietin in human sperm. According to the results of these studies, the erythropoietin takes part in the regulation of spermatogenesis, affecting the synthesis of hormones, in particular steroid ones. Currently, the physiological and pathogenetic effects of erythropoietin on human ejaculate have not been thoroughly studied. In this regard, the study of this protein in the ejaculate in patients with diseases of the male reproductive system, as well as in their absence, is relevant.The study objective is to determine the concentration of erythropoietin in ejaculate samples of healthy and men with oligoastenozoospermia.Materials and methods. Samples of ejaculate of 52 men of reproductive age were examined. The ejaculate was examined using the SQA-V sperm analyzer (MES, Israel). According to the results of the study, two groups were identified: the main group (n = 18) with reduced fertility and the control group (n = 34) with normal spermogram indicators. In seminal plasma samples, the concentration of erythropoietin was determined by solid-phase enzyme immunoassay using the test system “Erythropoietin-IFA-BEST” (A-8776) (Vector-best LLC, Russia).Results. Erythropoietin was detected in all ejaculate samples, the results ranged from 9.37 to 193.95 mME / ml and varied 20.7 times (p = 0.3). The median concentration in the main group was 64.49 mME / ml (41.96; 118.16 mME / ml) and 1.36 times higher than the results of the comparison group, which were 47.16 mME / ml (18.15; 90.94 mME / ml). No statistically significant regularities were found between the concentration of erythropoietin and the indicators of ejaculate fertility (r <|0,3|).Conclusion. In oligoastenozoospermia, there is a tendency to increase the content of erythropoietin in the seminal plasma, which requires further research, taking into account a more detailed stratification of the groups examined for reasons that caused a decrease in the number of spermatozoa.

Gut microbiota is an endocrine organ

The gut microbiota affects the processes of food digestion, intestinal peristalsis, controls the work of the intestinal epithelium, has protective properties against pathogenic microorganisms, activating local immunity and stimulating the secretion of mucus by intestinal cells. Besides the gut microbiota participates in the metabolism of proteins, fats and carbohydrates, mediates the processes of gluconeogenesis, glycogenolysis, lipogenesis and lipolysis, and affects on feelings of hunger and satiety. All these processes occur because the gut microbiota produces active metabolites throughout their life activity. Gut microbiota and active metabolites of the gut microbiota activate the synthesis of hormones. The gut microbiota affects the synthesis of hormones such as glucagon-like peptide-1, glucagon-like peptide-2, YY-peptide, glucose-dependent insu-linotropic peptide, ghrelin, leptin, cholecystokinin, serotonin, and insulin. Disturbance of the secretion of these hormones is one of the links in the pathogenesis of endocrine diseases such as diabetes and obesity. Thus, the gut microbiota is an endocrine organ. Changes in the composition and functions of the gut microbiota lead to metabolic disorders.This article describes the effect of gut germs and active metabolites of the gut microbiota on the synthesis hormones by means of receptor mechanisms, genes, and enzymes.

Recombinant production of eukaryotic cytochrome P450s in microbial cell factories

Cytochrome P450s (P450s) comprise one of the largest known protein families. They occur in every kingdom of life and catalyze essential reactions, such as carbon source assimilation, synthesis of hormones and secondary metabolites, or degradation of xenobiotics. Due to their outstanding ability of specifically hydroxylating complex hydrocarbons, there is a great demand to use these enzymes for biocatalysis, including applications at an industrial scale. Thus, the recombinant production of these enzymes is intensively investigated. However, especially eukaryotic P450s are difficult to produce. Challenges are faced due to complex cofactor requirements and the availability of a redox-partner (cytochrome P450 reductase, CPR) can be a key element to get active P450s. Additionally, most eukaryotic P450s are membrane bound which complicates the recombinant production. This review describes current strategies for expression of P450s in the microbial cell factories Escherichia coli, Saccharomyces cerevisiae, and Pichia pastoris.

Impact of salt stress, cell death, and autophagy on peroxisomes: quantitative and morphological analyses using small fluorescent probe N-BODIPY

Plant peroxisomes maintain a plethora of key life processes including fatty acid β-oxidation, photorespiration, synthesis of hormones, and homeostasis of reactive oxygen species (ROS). Abundance of peroxisomes in cells is dynamic; however mechanisms controlling peroxisome proliferation remain poorly understood because measuring peroxisome abundance is technically challenging. Counting peroxisomes in individual cells of complex organs by electron or fluorescence microscopy is expensive and time consuming. Here we present a simple technique for quantifying peroxisome abundance using the small probe Nitro-BODIPY, which in vivo fluoresces selectively inside peroxisomes. The physiological relevance of our technique was demonstrated using salinity as a known inducer of peroxisome proliferation. While significant peroxisome proliferation was observed in wild-type Arabidopsis leaves following 5-hour exposure to NaCl, no proliferation was detected in the salt-susceptible mutants fry1-6, sos1-14, and sos1-15. We also found that N-BODIPY detects aggregation of peroxisomes during final stages of programmed cell death and can be used as a marker of this stage. Furthermore, accumulation of peroxisomes in an autophagy-deficient Arabidopsis mutant atg5 correlated with N-BODIPY labeling. In conclusion, the technique reported here enables quantification of peroxisomes in plant material at various physiological settings. Its potential applications encompass identification of genes controlling peroxisome homeostasis and capturing stress-tolerant genotypes.

The role of inflammation in the pathogenesis of chronic heart failure

The review considers the main points of the concept of progressive chronic heart failure (CHF). The neurohumoral model of CHF pathogenesis could create novel approaches to treating these patients. However, recent studies have shown that the ways of activating the neurohumoral systems in CHF are much more complex. The increased local synthesis of hormones causes the activation of proinflammatory cytokines and proto-oncogenes, which have a number of negative effects. Multiple studies have formulated the immunoinflammatory concept of CHF pathogenesis, according to which the increased concentration of interleukin-6 is a marker of poor prognosis in CHF, and the level of tumor necrosis factor-α directly correlates with the severity of its clinical manifestations and the activity of the neurohumoral background in decompensation. The review gives a classification of cytokines and describes the reasons for their elevated plasma concentration, their possible role in the occurrence and progression of CHF, and their prognostic significance. The pathogenesis of CHF, which includes cytokine aggression, requires further studies of the effect of the inflammatory component on the course of heart failure.

Detemir (Levemir): modern paradigms of insulin therapy

Peculiarities of the molecular structure of Levemir (detemir) account for low variability of its pharmacodynamic properties and are responsible for the more predictable hypoglycemic effect and the lower risk of general and nocturnal hypoglycemic episodes in different age-groups of the patents suffering type 1 and 2 diabetes mellitus compared with other preparations of basal insulin. Moreover, insulin detemir (Levemir) does not affect the body weight of the patients due to its central action (rapid penetration across the hematoencephalic barrier, control of hunger and satiation, improved recognition of hypoglycemic states) and the influence on the synthesis of hormones regulating appetite and energy metabolism. Insulin detemir is shown to possess neurotropic properties, such as hepato-selective action on the liver, lipid metabolism, and sodium re-absorption.