Low levels of vitamin D in population exposed to significant environmental pollution.

In recent years, monitoring of vitamin D levels and possible use of supplementation is gaining attention. Numerous studies showed low levels of vitamin D in winter months followed by improvement during summer. These changes are mostly dependent on the level of sun exposure, but also on geographical location, genetic factors, social-economic status, quality of nutrition and environmental pollution. In this observation we found significant decrease in vitamin D levels in populations exposed to extreme environmental pollution in area of central Europe. This region is known for extreme burden from microparticles originating in chemical industry, surface coal mining and cold-based power stations. Vitamin D levels in all patients was determined by ELISA. Using 540 patients in our department of clinical immunology and allergology we measured the levels of vitamin D in 2016 to 2021 period. In only 4 patients (0.74 %) we found vitamin D levels higher than 30 ng/ml. The curve of observed values does not reflect dependency on sun exposure and does not change during the year. We discuss the effect of environmental contaminants, lifestyle and economic and social factors. From our observations, we propose to directly supplement population with vitamin D, particularly children and seniors. From our observations, we propose to directly supplement population with vitamin D, particularly children and seniors.

Delayed ejaculation in men with depressive disorders.

Delayed ejaculation belongs to the group of sexual disorders in men. The causes of delayed ejaculation or anejaculation are not exactly known. It is assumed that it can be caused by psychogenic or organic influences or their combinations. One of the causes of delayed ejaculation may be elevated prolactin levels, which may be increased by psychosocial stress, pituitary disorders or also treatment with selective serotonin reuptake inhibitors in the treatment of depression. We tested a selected group of 50 men who were diagnosed with a depressive disorder and whose antidepressant treatment lasted for at least 24 weeks. These patients reported long-term delayed ejaculation or, in some cases, anejaculation as comorbidity. The results showed significant Spearman's correlation between elevated prolactin levels and intravaginal ejaculation latency values (R = 0.45), as well as between Beck's Depression-II inventory and intravaginal ejaculation latency and latency values (R = 0.48).

Trained Immunity as an Adaptive Branch of Innate Immunity.

The concept of trained immunity has become one of the most interesting and potentially commercially and clinically relevant ideas of current immunology. Trained immunity is realized by the epigenetic reprogramming of non-immunocompetent cells, primarily monocytes/macrophages and natural killer (NK) cells, and is less specific than adaptive immunity; therefore, it may cross-protect against other infectious agents. It remains possible, however, that some of the observed changes are simply caused by increased levels of immune reactions resulting from supplementation with immunomodulators, such as glucan. In addition, the question of whether we can talk about trained immunity in cells with a life span of only few days is still unresolved.

Sulfonated and Carboxymethylated ß-Glucan Derivatives with Inhibitory Activity against Herpes and Dengue Viruses.

The infection of mammalian cells by enveloped viruses is triggered by the interaction of viral envelope glycoproteins with the glycosaminoglycan, heparan sulfate. By mimicking this carbohydrate, some anionic polysaccharides can block this interaction and inhibit viral entry and infection. As heparan sulfate carries both carboxyl and sulfate groups, this work focused on the derivatization of a (1→3)(1→6)-ß-D-glucan, botryosphaeran, with these negatively-charged groups in an attempt to improve its antiviral activity. Carboxyl and sulfonate groups were introduced by carboxymethylation and sulfonylation reactions, respectively. Three derivatives with the same degree of carboxymethylation (0.9) and different degrees of sulfonation (0.1; 0.2; 0.4) were obtained. All derivatives were chemically characterized and evaluated for their antiviral activity against herpes (HSV-1, strains KOS and AR) and dengue (DENV-2) viruses. Carboxymethylated botryosphaeran did not inhibit the viruses, while all sulfonated-carboxymethylated derivatives were able to inhibit HSV-1. DENV-2 was inhibited only by one of these derivatives with an intermediate degree of sulfonation (0.2), demonstrating that the dengue virus is more resistant to anionic ß-D-glucans than the Herpes simplex virus. By comparison with a previous study on the antiviral activity of sulfonated botryosphaerans, we conclude that the presence of carboxymethyl groups might have a detrimental effect on antiviral activity.

Review: ß-glucans as Effective Antibiotic Alternatives in Poultry.

The occurrence of microbial challenges in commercial poultry farming causes significant economic losses. Antibiotics have been used to control diseases involving bacterial infection in poultry. As the incidence of antibiotic resistance turns out to be a serious problem, there is increased pressure on producers to reduce antibiotic use. With the reduced availability of antibiotics, poultry producers are looking for feed additives to stimulate the immune system of the chicken to resist microbial infection. Some ß-glucans have been shown to improve gut health, to increase the flow of new immunocytes, increase macrophage function, stimulate phagocytosis, affect intestinal morphology, enhance goblet cell number and mucin-2 production, induce the increased expression of intestinal tight-junctions, and function as effective anti-inflammatory immunomodulators in poultry. As a result, ß-glucans may provide a new tool for producers trying to reduce or eliminate the use of antibiotics in fowl diets. The specific activity of each ß-glucan subtype still needs to be investigated. Upon knowledge, optimal ß-glucan mixtures may be implemented in order to obtain optimal growth performance, exert anti-inflammatory and immunomodulatory activity, and optimized intestinal morphology and histology responses in poultry. This review provides an extensive overview of the current use of ß glucans as additives and putative use as antibiotic alternative in poultry.

Endometriosis and gynaecological cancers: molecular insights behind a complex machinery.

Endometriosis is described as the presence of both endometrial glandular and stromal cells outside the uterine cavity. A major characterization of this disease is ectopic implantation of endometrial cells with increased migration. It is one of the leading causes of morbidity among premenopausal women, with a prevalence of 10-16% of women of reproductive age. Despite over century of intensive research, none of the current treatment options represents a real cure. Based on the current knowledge, endometriosis, particularly its atypical version, is considered to be a transitional form from benign disease to tumour. However, the exact mechanisms of this conversion are still not fully established.

ß-glucan as a new tool in vaccine development.

Vaccination constitutes one of the major breakthroughs in human medicine. At the same time, development of more immunogenic vaccine alternatives to using aluminium-based adjuvants is one of the most important phases of vaccination development. Among different sources of carbohydrate polymers, including plants, microbes and synthetic sources tested, glucans were found to be the most promising vaccine adjuvant, as they alone stimulate various immune reactions including antibody production without any negative side effects. The use of glucan particles as a delivery system is a viable option based on the documented efficient antigen loading and receptor-targeted uptake in antigen-presenting cells. In addition to particles, soluble glucans can be used as novel hydrogels or as direct immunocyte-targeting delivery systems employing novel complexes with oligodeoxynucleotides. This review focuses on recent advances in glucan-based vaccine development from glucan-based conjugates to a glucan-based delivery and adjuvant platform.

Endometriosis and risk of ovarian cancer: what do we know?

PURPOSE: Despite long and intensive research, endometriosis remains one of the leading causes of morbidity among premenopausal women. The majority of endometriosis-related ovarian carcinomas occur in the presence of atypical ovarian endometriosis. Nevertheless, despite the increased incidence of ovarian cancer in patients with endometriosis, our knowledge of the risk factors and mechanisms is still incomplete. METHOD: Narrative overview, synthesizing the recent findings of literature retrieved from databases. RESULTS: Herein, we reviewed and summarized the most recent knowledge regarding endometriosis and ovarian cancer. CONCLUSION: The evidence showing that patients with endometriosis have a higher risk of developing ovarian cancer is compelling. However, the question of how much higher the absolute risk is, is not fully clear.

Lysosomotropic Features and Autophagy Modulators among Medical Drugs: Evaluation of Their Role in Pathologies.

The concept of lysosomotropic agents significantly changed numerous aspects of cellular biochemistry, biochemical pharmacology, and clinical medicine. In the present review, we focused on numerous low-molecular and high-molecular lipophilic basic compounds and on the role of lipophagy and autophagy in experimental and clinical medicine. Attention was primarily focused on the most promising agents acting as autophagy inducers, which offer a new window for treatment and/or prophylaxis of various diseases, including type 2 diabetes mellitus, Parkinson's disease, and atherosclerosis. The present review summarizes current knowledge on the lysosomotropic features of medical drugs, as well as autophagy inducers, and their role in pathological processes.

Hypolipidemic Effects of ß-Glucans, Mannans, and Fucoidans: Mechanism of Action and Their Prospects for Clinical Application.

The search for lipid-lowering drugs is important for clinical medicine. This review summarizes our research findings regarding the hypolipidemic activity of polysaccharides. There are several validated agents altering lipid levels which reduce the risk of atherosclerotic cardiovascular events. Nonetheless, for many people, the risk of such an event remains unacceptably high despite treatment with these agents. This situation has prompted the search for new therapies to reduce the residual cardiovascular risk. The lipid-lowering effect of ß-glucans consumed with food was demonstrated in patients with atherosclerosis. The mechanism of the protective effect of ß-glucans is poorly studied. The effects of ß-glucans are mediated by Toll-like receptors, by dectin-1, and possibly by other receptors. Nevertheless, the mechanism of the protective action of ß-glucan in lipemic mice has been studied insufficiently. This review will present up-to-date information regarding experimental hypolipidemic polysaccharide compounds that hold promise for medicine. Phagocyte-specific chitotriosidase in humans contributes to innate immune responses against chitin-containing fungi. This enzyme has been first described in patients with Gaucher disease and serves as an important diagnostic biomarker. It has been reported that, in mice, chitin particles of certain size are recognized by macrophages through Toll-like receptors, dectin-1, and to a lesser extent through mannose receptor.

Development of Fish Immunity and the Role of ß-Glucan in Immune Responses.

Administration of ß-glucans through various routes, including immersion, dietary inclusion, or injection, have been found to stimulate various facets of immune responses, such as resistance to infections and resistance to environmental stress. ß-Glucans used as an immunomodulatory food supplement have been found beneficial in eliciting immunity in commercial aquaculture. Despite extensive research involving more than 3000 published studies, knowledge of the receptors involved in recognition of ß-glucans, their downstream signaling, and overall mechanisms of action is still lacking. The aim of this review is to summarize and discuss what is currently known about of the use of ß-glucans in fish.

Synthesis and Evaluation of Oligomeric Thioether-Linked Carbacyclic ß-(1→3)-Glucan Mimetics.

Extrapolating from lessons learnt with previous low-molecular-weight ß-(1→3)-glucan mimetics, we designed a series of minimal 2,4-dideoxy-thioether-linked carbacyclic ß-(1→3)-glucan mimetics and synthesized di-, tri-, and tetramers in an enantiomerically pure form by an iterative sequence based on a simple building block readily available from commercial ( S)-(-)-3-cyclohexenecarboxylic acid. These substances were screened for their ability to inhibit anti-CR3-fluorescein isothiocyanate (FITC) staining of human neutrophils and anti-Dectin-1-FITC staining of mouse macrophages as well as for their ability to stimulate phagocytosis and pinocytosis. In each assay, the synthetic compounds displayed comparable activity to the corresponding native ß-(1→3)-glucans, laminaritriose, and tetraose, suggesting that the exploitation of hydrophobic patches in the lectin-binding domains of CR3 and Dectin-1 is a promising strategy for the development of small-molecule analogues of ß-(1→3)-glucans.

Glucan and Mannan-Two Peas in a Pod.

In recent decades, various polysaccharides isolated from algae, mushrooms, yeast, and higher plants have attracted serious attention in the area of nutrition and medicine. The reasons include their low toxicity, rare negative side effects, relatively low price, and broad spectrum of therapeutic actions. The two most and best-studied polysaccharides are mannan and glucan. This review focused on their biological properties.

Fungal Exocellular (1-6)-ß-d-glucan: Carboxymethylation, Characterization, and Antioxidant Activity.

Exocellular (1→6)-ß-d-glucan (lasiodiplodan) produced by the fungus Lasiodiplodia theobromae MMPI was derivatized by carboxymethylation using different concentrations of a derivatizing agent. Lasiodiplodan was derivatized by carboxymethylation in an attempt to increase its solubility and enhance its biological activities. Carboxymethylglucans with degrees of substitution (DS) of 0.32, 0.47, 0.51, 0.58, and 0.68 were produced and characterized. FTIR analysis showed a band of strong intensity at 1600 cm-1 and an absorption band at 1421 cm-1, resulting from asymmetric and symmetrical stretching vibrations, respectively, of the carboxymethyl group COO- in the carboxymethylated samples. Thermal analysis showed that native lasiodiplodan (LN) and carboxymethylated derivatives (LC) exhibited thermal stability up to 200-210 °C. X-ray diffractometry demonstrated that both native and carboxymethylated lasiodiplodan presented predominantly an amorphous nature. Scanning electron microscopy revealed that carboxymethylation promoted morphological changes in the biopolymer and increased porosity, and alveolar structures were observed along the surface. The introduction of carboxymethyl groups in the macromolecule promoted increased solubility and potentiated the hydroxyl radical-scavenging activity, suggesting a correlation between degree of substitution and antioxidant activity.

Beta Glucan: Supplement or Drug? From Laboratory to Clinical Trials.

Glucans are part of a group of biologically active natural molecules and are steadily gaining strong attention not only as an important food supplement, but also as an immunostimulant and potential drug. This paper represents an up-to-date review of glucans (ß-1,3-glucans) and their role in various immune reactions and the treatment of cancer. With more than 80 clinical trials evaluating their biological effects, the question is not if glucans will move from food supplement to widely accepted drug, but how soon.

Encapsulated Microparticles of (1→6)-ß-d-Glucan Containing Extract of Baccharis dracunculifolia: Production and Characterization.

ß-Glucans are biomacromolecules well known, among other biological activities, for their immunomodulatory potential. Similarly, extracts of Baccharis dracunculifolia also possess biological properties and are used in folk medicine for the treatment of inflammation, ulcers, and hepatic diseases. Microparticles containing (1→6)-ß-d-glucan (lasiodiplodan) and B. dracunculifolia extract were produced and characterized. A 23 factorial design was employed to define the conditions of production of microparticles by atomization. Lasiodiplodan associated with maltodextrin and gum arabic was studied as a matrix material. Microparticles of 0.4 µm mean size and high phenolics content (3157.9 µg GAE/g) were obtained under the optimized conditions. The microparticle size ranged from 0.23 to 1.21 µm, and the mathematical model that best represented the release kinetics of the extract was the Korsmeyer-Peppas model. Diffusional exponent (n) values of 0.64 at pH 7.7 and 1.15 at pH 2.61 were found, indicating particles with a non-Fickian or anomalous transport system, and Super Case II transport, respectively. Thermal analysis indicated that the microparticles demonstrated high thermal stability. The X-ray diffraction analyses revealed an amorphous structure, and HPLC-DAD analysis showed microparticles rich in phenolic compounds: caffeic acid, p-coumaric acid, and catechin. The microparticles obtained comprise a new biomaterial with biological potential for applications in different fields.

Synthesis and Evaluation of 1,5-Dithia-d-laminaribiose, Triose, and Tetraose as Truncated ß-(1→3)-Glucan Mimetics.

The preparation and characterization of a series of di-, tri-, and tetrasaccharide analogues of ß-(1→3)-glucans is described in which each pyranoside ring is replaced by a 5-thiopyranosyl ring and each glycosidic oxygen by a thioether. These oligomeric 1,5-dithio-d-glucopyranose derivatives were shown to inhibit the staining of human neutrophils and of mouse macrophages by fluorescent anti-CR3 and anti-Dectin-1 antibodies, respectively. The compounds were also demonstrated to stimulate phagocytosis and pinocytosis indicative of binding to the carbohydrate binding domains of complement receptor 3 (CR3) and Dectin-1. Activity in all three assays was optimum at the level of the trisaccharide mimic, suggesting that, while the replacement of ethereal oxygens by thioethers results in a greater affinity for the aromatic lined hydrophobic binding pockets, the presence of multiple longer C-S bonds eventually results in a mismatch and a loss of affinity.

Biological Markers of Oxidative Stress in Cardiovascular Diseases: After so Many Studies, What do We Know?

Numerous conditions, including cancer, diabetes, aging, and atherosclerosis, are thought to be associated with oxidative stress. Oxidative stress is defined as a persistent imbalance between oxidation and antioxidation, resulting in the damage of cellular macromolecules and is often considered to be involved in wide variety of human diseases. However, the current literature is very heterogeneous making it rather difficult to draw general conclusions. Often, different biomarkers have been used in different health problems. In addition, individual biomarkers are often measured using nonspecific methods. The development of informative and highly reliable markers is very important. The conflicting results of numerous studies, including clinical trials, make it clear that despite the explosion of studies performed in the last decades, leading to nutritional guidelines recommending consumption of food-related antioxidants, direct proof is still lacking.

Altered Immunity in Endometriosis: What Came First?

BACKGROUND: This study was conducted to summarize current knowledge of the changes within the immune system, from action of macrophages, lymphocytes and NK cells to biological effects of their products. Endometriosis is a complex gynecological disorder defined as a presence of endometrial tissue outside the uterus affecting over 5 million reproductive-aged women in the U.S. alone. RESULT: In recent years, the potential role of the immune system in the development of endometriosis has increasingly gained attention. Data summarized in our study showed that the most relevant immunocytes are macrophages residing inside the peritoneal cavity and the ratios of Th1 to Th2 cells. Another crucial immunological parameter is the balance in production of cytokines and chemoatractants. CONCLUSIONS: This review confirms that despite decades of intensive research, the involvement of the immune system remains elusive, as we can recognize the changes, but still do not understand if these changes represent the results of endometriosis or if they are contributing factors. Based on these findings, we also discuss new treatment possibilities.

Spatial Distribution of Glucan Type and Content between Caps and Stalks in Pleurotus eryngii: Impact on the Anti-inflammatory Functionality.

: Pleurotus eryngii is recognized for its prominent nutritional and medicinal value. In our study, we tested the effect of glucans on lipopolysaccharide (LPS)-induced production of TNF-α. We demonstrated that glucan extracts are more effective than mill mushroom preparations. Additionally, the effectiveness of stalk-derived glucans were slightly more pronounced than of caps. Cap and stalk glucans from mill or isolated glucan competed dose-dependently with anti-Dectin-and anti-CR-3 antibodies, indicating that they contain ß-glucans recognized by these receptors. Using the dextran sulfate sodium (DSS)-inflammatory bowel disease mice model, intestinal inflammatory response to the mill preparations was measured and compared to extracted glucan fractions from caps and stalks. We found that mill and glucan extracts were very effective in downregulating IFN-γ and MIP-2 levels and that stalk-derived preparations were more effective than from caps. The tested glucans were equally effective in regulating the number of CD14/CD16 monocytes and upregulating the levels of fecal-released IgA to almost normal levels. In conclusion, the most effective glucans in ameliorating some IBD-inflammatory associated symptoms induced by DSS treatment in mice were glucan extracts prepared from the stalk of P. eryngii. These spatial distinctions may be helpful in selecting more effective specific anti-inflammatory mushrooms-derived glucans.