Tissue immunoexpression of IL-6 and IL-18 in aging men with BPH and MetS and their relationship with lipid parameters and gut microbiota-derived short chain fatty acids.

Recent studies indicate that inflammation is one of the causes of the development of benign prostatic hyperplasia (BPH). Inflammation may result from past infections, metabolic disorders, but also from the state of functioning of the intestinal microbiota. The aim of the study was to assess whether the diagnostic lipid parameters for metabolic syndrome and short-chain fatty acids (SCFAs) are related to the immunoexpression of interleukins in prostate tissue with benign hyperplasia. The study involved 103 men with BPH, who were divided into two groups depending on the presence of MetS. We analysed tissue immunoexpression of two proinflammatory interleukins: IL-6, which is known to be involved in the development of BPH, and IL-18, which has not been analysed so far. The results of our study indicate that men with BPH + MetS in the stroma of the prostate have a significantly higher overall percentage of IL-6+ cells compared to men without MetS (p = 0.034). The analysis of IL-18 immunoexpression in prostate tissue indicated that in men with BPH + MetS, the glandular part of the prostate had a significantly higher percentage of cells with strong IL-18 expression (p = 0.040). We also noticed a relationship between tissue expression of IL-6 and IL-18 and lipid parameters (TG and HDL). We conclude that lipid disorders occurring in men with BPH increase inflammation in the prostate gland. Moreover, it has also been demonstrated for the first time that, indirectly, through SCFAs, the gut microbiota can act to prevent or create an inflammatory microenvironment in the prostate gland.

Heat Shock Proteins in Benign Prostatic Hyperplasia and Prostate Cancer.

Two out of three diseases of the prostate gland affect aging men worldwide. Benign prostatic hyperplasia (BPH) is a noncancerous enlargement affecting millions of men. Prostate cancer (PCa) in turn is the second leading cause of cancer death. The factors influencing the occurrence of BPH and PCa are different; however, in the course of these two diseases, the overexpression of heat shock proteins is observed. Heat shock proteins (HSPs), chaperone proteins, are known to be one of the main proteins playing a role in maintaining cell homeostasis. HSPs take part in the process of the proper folding of newly formed proteins, and participate in the renaturation of damaged proteins. In addition, they are involved in the transport of specific proteins to the appropriate cell organelles and directing damaged proteins to proteasomes or lysosomes. Their function is to protect the proteins against degradation factors that are produced during cellular stress. HSPs are also involved in modulating the immune response and the process of apoptosis. One well-known factor affecting HSPs is the androgen receptor (AR)-a main player involved in the development of BPH and the progression of prostate cancer. HSPs play a cytoprotective role and determine the survival of cancer cells. These chaperones are often upregulated in malignancies and play an indispensable role in tumor progression. Therefore, HSPs are considered as one of the therapeutic targets in anti-cancer therapies. In this review article, we discuss the role of different HSPs in prostate diseases, and their potential as therapeutic targets.

Alterations in fecal short chain fatty acids (SCFAs) and branched short-chain fatty acids (BCFAs) in men with benign prostatic hyperplasia (BPH) and metabolic syndrome (MetS).

Gut microbiome-derived short-chain fatty acids (SCFAs) emerge in the process of fermentation of polysaccharides that resist digestion (dietary fiber, resistant starch). SCFAs have a very high immunomodulatory potential and ensure local homeostasis of the intestinal epithelium, which helps maintain the intestinal barrier. We analyzed the association between stool SCFAs levels acetic acid (C 2:0), propionic acid (C 3:0), isobutyric acid (C 4:0i), butyric acid (C 4:0n), isovaleric acid (C 5:0i) valeric acid (C 5:0n), isocaproic acid (C 6:0i), and caproic acid (C 6:0n)) in aging man with benign prostatic hyperplasia (BPH) and healthy controls. The study involved 183 men (with BPH, n = 103; healthy controls, n = 80). We assessed the content of SCFAs in the stool samples of the study participants using gas chromatography. The levels of branched SCFAs (branched-chain fatty acids, BCFAs): isobutyric acid (C4:0i) (p = 0.008) and isovaleric acid (C5:0i) (p < 0.001) were significantly higher in patients with BPH than in the control group. In healthy participants isocaproic acid (C6:0i) predominated (p = 0.038). We also analyzed the relationship between stool SCFA levels and serum diagnostic parameters for MetS. We noticed a relationship between C3:0 and serum lipid parameters (mainly triglycerides) in both healthy individuals and patients with BPH with regard to MetS. Moreover we noticed relationship between C4:0i, C5:0i and C6:0i and MetS in both groups. Our research results suggest that metabolites of the intestinal microflora (SCFAs) may indicate the proper function of the intestines in aging men, and increased BCFAs levels are associated with the presence of BPH.

Influence of metabolic syndrome on the relationship between fatty acids and the selected parameters in men with benign prostatic hyperplasia.

The purpose of our investigation was to analyze the relationship between the serum levels of fatty acids and their metabolites and the levels of the selected metabolic and hormonal parameters in patients with benign prostatic hyperplasia (BPH) with regard to concomitant metabolic syndrome (MetS). We determined serum concentrations of total (TT) and free testosterone (FT), insulin (I), dehydroepiandrosterone sulphate (DHEAS), luteinizing hormone and insulin-like growth factor 1 (IGF-1) and sex hormone-binding globulin (SHBG). Gas chromatography was performed. The patients differed in terms of hormone levels, but only the differences in SHBG and IGF-1 levels were statistically significant. Analysis of the levels of polysaturated fatty acids in BPH patients showed that MetS contributed to changes in the levels of these acids. We also analyzed the relationship between the levels of fatty acids and diagnostic parameters for MetS. Particular abnormalities were associated with single changes in the levels of fatty acids. In the diabetic patients, changes in the levels of pentadecanoic acid, heptadecanoic acid and cis-11-eicosenoic acid were demonstrated. Our findings indicate the necessity for further investigation concerning the levels of fatty acids and their impact on the development of MetS, as well as the course and clinical picture of BPH.

The Relationship between Eicosanoid Levels and Serum Levels of Metabolic and Hormonal Parameters Depending on the Presence of Metabolic Syndrome in Patients with Benign Prostatic Hyperplasia.

Background: The purpose of our investigation was to analyze the relationship between the serum levels of inflammatory mediators (HETE, HODE) and the levels of selected metabolic and hormonal parameters in patients with benign prostatic hyperplasia (BPH) with regard to concomitant metabolic syndrome (MetS). Methods: The study involved 151 men with BPH. Blood samples were taken for laboratory analysis of the serum levels of metabolic and hormonal parameters. Gas chromatography was performed using an Agilent Technologies 7890A GC System. Results: We found that waist circumference was the only parameter related to the levels of fatty acids, namely: 13(S)-HODE, 9(S)-HODE, 15(S)-HETE, 12(S)-HETE, and 5-HETE. In the patients with BPH and MetS, triglycerides correlated with 9(S)-HODE, 15(S)-HETE, 12(S)-HETE, and 5-HETE, which was not observed in the patients without MetS. Similarly, total cholesterol correlated with 9(S)-HODE, and 15(S)-HETE in the patients with BPH and MetS, but not in those without MetS. In the group of BPH patients with MetS, total testosterone positively correlated with 13(S)-HODE, and free testosterone with 9(S)-HODE. Conclusions: Based on this study, it can be concluded that lipid mediators of inflammation can influence the levels of biochemical and hormonal parameters, depending on the presence of MetS in BPH patients.

Immunomodulatory potential of gut microbiome-derived short-chain fatty acids (SCFAs).

Intestinal microbiota is an element of the bacterial ecosystem in all mammalian organisms. These microorganisms play a very important part in the development, functioning, and modulation of the immune system from the moment of birth. In recent years, owing to the use of modern sequencing techniques, the microbiome composition in healthy people has been identified based on bacterial 16S rRNA analysis. Currently, more and more attention is being given to the influence of microorganisms on the host's cellular metabolism. Analysis of microbial metabolites, among them short-chain fatty acids (SCFAs), and disruption of intestinal microbiota homeostasis in terms of their effects on molecular regulatory mechanisms of immune reactions will surely improve the understanding of the etiology of many common diseases. SCFAs, mainly butyrate, propionate, and acetate, occur in specific amounts, and their proportions can change, depending on the diet, age and diseases. The levels of SCFAs are substantially influenced by the ratio of commensal intestinal bacteria, the disturbance of which (dysbiosis) can lead to a disproportion between the SCFAs produced. SCFAs are regarded as mediators in the communication between the intestinal microbiome and the immune system. The signal they produce is transferred, among others, in immune cells via free fatty acid receptors (FFARs), which belong to the family of G protein-coupled receptors (GPCRs). It has been also confirmed that SCFAs inhibit the activity of histone deacetylase (HDAC) - an enzyme involved in post-translational modifications, namely the process of deacetylation and, what is new, the process of histone crotonylation. These properties of SCFAs have an effect on their immunomodulatory potential i.e. maintaining the anti/pro-inflammatory balance. SCFAs act not only locally in the intestines colonized by commensal bacteria, but also influence the intestinal immune cells, and modulate immune response by multi-protein inflammasome complexes. SCFAs have been confirmed to contribute to the maintenance of the immune homeostasis of the urinary system (kidneys), respiratory system (lungs), central nervous system, and the sight organ.

Assessment of morphological changes and steroid receptors in the uteri of postmenopausal women.

INTRODUCTION: The morphology of the endometrium constantly changes in the reproductive period, depending on the levels of ovarian steroid hormones, and undergoes atrophic changes during menopause as a result of their insufficiency. The purpose of this study was to analyze morphological and morphometric changes in the mucous and muscle layers of the uterine wall in postmenopausal women, and to assess localization and number of cells showing the expression of steroid hormone receptors, namely estrogen receptor α (ER-α), progesterone receptor (PR), and androgen receptor (AR) in glandular epithelial cells and smooth muscle cells in particular groups of women. MATERIAL AND METHODS: The study material consisted of uterine specimens sectioned across the full thickness of the uterine wall, and embedded in 164 paraffin blocks. The specimens came from women without menopausal hormone therapy (MHT) operated due to reproductive organ prolapse or uterine myomas. The material was divided into four groups depending on the time interval from menopause to surgery: group I - from 1 to 5 years after menopause, group II - from 6 to 10 years after menopause, group III - more than 11 years after menopause, and group IV - women over 70 years of age. The sections were stained by standard HE, Masson's trichrome, and immunohistochemical methods (ERα, PR, AR). Quantitative assessment of the results was based on computer image analysis. RESULTS: Analysis of morphological changes in the endometrium and myometrium revealed the presence of increasing regressive changes, such as various types of atrophy, fibrosis, and calcification, augmented over time from the last menstruation. Furthermore, endometrial polyps, foci of endometriosis, and leiomyomas were observed. Based on the results of morphometric measurements, a constant decrease in the endometrial and myometrial thickness was noticed in the studied groups (I-IV). Significant differences between the groups were observed in the number of ER-α positive cells in the myometrium, but not in the endometrial glandular epithelium. Statistically significant differences in the number of AR positive cells were detected in the endometrial epithelium and in the uterine muscle. The analysis the number of PR positive cells demonstrated differences between the groups in the endometrial stroma and the myometrium. CONCLUSION: The uterus of postmenopausal woman undergo major morphological changes (mainly atrophic lesions in the endometrium and myometrium), leading to a decline in their morphometric parameters over time from the last menstruation. Localization and number of cells showing the expression of steroid receptors: ER-α, PR, and AR in the uterus of postmenopausal women, depending on the time interval from the last menstruation.

Comparison between selected hormone and protein levels in serum and prostate tissue homogenates in men with benign prostatic hyperplasia and metabolic disorders.

PURPOSE: The purpose of the study was to assess the relationship between changes in the levels of selected hormones in serum and prostate tissue homogenate in regard to metabolic disorders in patients with diagnosed, surgically treated benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: The study involved a group of 154 men with a diagnosis of BPH with metabolic syndrome (MetS) and without MetS. The serum levels of the hormones - total testosterone, free testosterone, insulin, dehydroepiandrosterone sulfate, estradiol, luteinizing hormone, sex hormone binding globulin (SHBG), and insulin-like growth factor-1 (IGF-1) - were determined using the ELISA method. Prostate tissue sections obtained from the patients during transurethral resection of the prostate were frozen in liquid nitrogen. We determined the levels of the same hormones. RESULTS: There was a statistically significant difference between the groups in terms of serum SHBG levels, but not in the prostate tissue SHBG levels. A similar relationship was observed in regard to IGF-1, the serum levels of which were significantly higher in patients with MetS. MetS had an effect on the ratio of hormone levels in serum to their levels in the prostate tissue. Correlations between the levels of biochemical parameters and the levels of hormones in serum and the prostate tissue of BPH patients with and without MetS demonstrate that serum SHBG levels correlated weakly with waist size and triglyceride levels. CONCLUSION: The occurrence of MetS in BPH patients was associated with changes in the levels of hormones and proteins. These changes, however, were not always equivalent to changes in the levels of these parameters in prostate tissue. It should also be mentioned that MetS in BPH patients had an influence on a quantitative balance between the levels of SHBG in serum and prostate tissue.

Immunological memory cells.

This article reviews immunological memory cells, currently represented by T and B lymphocytes and natural killer (NK) cells, which determine a rapid and effective response against a second encounter with the same antigen. Among T lymphocytes, functions of memory cells are provided by their subsets: central memory, effector memory, tissue-resident memory, regulatory memory and stem memory T cells. Memory T and B lymphocytes have an essential role in the immunity against microbial pathogens but are also involved in autoimmunity and maternal-fetal tolerance. Furthermore, the evidence of immunological memory has been established for NK cells. NK cells can respond to haptens or viruses, which results in generation of antigen-specific memory cells. T, B and NK cells, which have a role in immunological memory, have been characterized phenotypically and functionally. During the secondary immune response, these cells are involved in the reaction against foreign antigens, including pathogens, and take part in autoimmune diseases, but also are crucial to immunological tolerance and vaccine therapy.

Mechanisms of type I interferon action and its role in infections and diseases transmission in mammals.

Interferons (IFNs) are pivotal regulators of immunological processes. This paper describes mainly type I interferons -α and -ß and their recently recounted signaling pathways, especially connected with ISGs - interferon stimulated genes, having a crucial role in regulating IFN recruitment. Moreover, the paper shows the data on the role of interferons -α and -ß in infections - not only commonly known viral infections, but also bacterial, fungal and parasitic.