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).

The Search for Biomarkers in Endometriosis: a Long and Windy Road.

Endometriosis is a complex and chronic estrogen-dependent disease, affecting a significant proportion of women of reproductive age. Despite the long interest and extensive research, the pathogenesis of the disease is still debated. Although available non-invasive diagnostic methods have adequate accuracy, an invasive approach by laparoscopy is often necessary to obtain histological confirmation. In this scenario, the search for an accurate, reliable, cost-effective, clinically applicable non-invasive biomarker plays a crucial role in a potentially early diagnosis and, in this way, shape the future management of the disease. Considering these elements, the current review aims to summarize the most significant and novel results about biomarkers for the diagnosis and follow-up of women affected by endometriosis.

Beta-glucans induce cellular immune training and changes in intestinal morphology in poultry.

Introduction: Beta-glucans are known as biological response modifiers due to their ability to activate the immune system. This research aimed to determine the efficacy and safety of feeding beta-glucans from various sources on the immune status and intestinal morphology of chickens. Methods: To this end we used in vitro and in vivo set-ups. In the in vitro set-up the chicken macrophage cell line HD-11 was used to measure the response of the chicken immune cells to beta-glucans extracted from algae and mushrooms on immune-related gene expression and associated activities. Additionally, we conducted two in vivo experiments using either beta-glucans extracted from yeast or mix of yeast and mushrooms beta-glucans as part of the chicks feed in order to test their effects on the chick intestinal morphology. Results: In the in vitro set-up exposure of HD-11 cells to a concentration of 1 mg/ml of algae and mushroom beta-glucans resulted in significantly higher expression of 6 genes (TNFα, IL4, IL6, IL8, IL10, and iNOS2) compared to control. The release of nitrite oxide (NO) to the medium after exposure of HD-11 cells to mushrooms or algae beta-glucans was significantly increased compared to control. Additionally, significantly increased phagocytosis activity was found after exposure of the cells to algae and mushroom beta-glucans. In the in vivo set-up we observed that the length of the villi and the number of goblet cells in the ileum and the jejunum in the beta-glucan fed chicks were significantly augmented compared to control, when the chicks were fed with either yeast or yeast and mushroom beta-glucans mix. Discussion: In conclusion, dietary supplementation of poultry with beta-glucan exerts significant and positive effects on immune activity and the intestinal morphology in poultry.

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.

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.

Biological properties of andrographolide, an active ingredient of Andrographis Paniculata: a narrative review.

Andrographolide is a labdane diterpenoid isolated from Andrographis paniculata and traditionally used in Chinese and Indian medicine. Reported effects include anti-bacterial, anti-inflammatory and anti-cancer functions. Most of the studies support the hypothesis that andrographolide supplementation stimulates immune system, so the observed effects migh in fact be secondary to the stimulation of defense reactions. As andrographolide is involved in regulation of inflammation, it is not surprising that it is also evaluated in inflammation-mediated diseases such as ulcerative colitis. Anticancer effects of the andrographolide have been tested on various cancer panels. Colon cancer, breast cancer, and head and neck carcinomas were the most investigated, followed by prostate cancer and glioblastoma. The results looked promising. However, problems with solubility and low level of active substance in natural extract leads to preparation of chemical analogs. Objective of this short review is to summarize current knowledge of the biological effects of andragrapholide. We conclude that despite documented effects and some partly characterized mechanisms of action, more research is clearly needed. At present, the doses, types of treatment and possible negative side effects are not yet established. In addition, various isolations and compound formulas have been used for treatment of various diseases, making final conclusions problematic.

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.

Effects of Medicinal Fungi-Derived ß-Glucan on Tumor Progression.

ß-Glucans have been studied in animal species, from earthworms to humans. They form a heterogenous group of glucose polymers found in fungi, plants, bacteria, and seaweed. ß-Glucans have slowly emerged as an important target for the recognition of pathogens. In the current review, we highlight the major roles of mushroom-derived ß-glucans on cancer progression.

Hepatocyte and immune cell crosstalk in non-alcoholic fatty liver disease.

Introduction: Nonalcoholic fatty liver disease (NAFLD) is the most widespread chronic liver disease in the world. It can evolve into nonalcoholic steatohepatitis (NASH) where inflammation and hepatocyte ballooning are key participants in the determination of this steatotic state.Areas covered: To provide a systematic overview and current understanding of the role of inflammation in NAFLD and its progression to NASH, the function of the cells involved, and the activation pathways of the innate immunity and cell death; resulting in inflammation and chronic liver disease. A PubMed search was made with relevant articles together with relevant references were included for the writing of this review.Expert opinion: Innate and adaptive immunity are the key players in the NAFLD progression; some of the markers presented during NAFLD are also known to be immunity biomarkers. All cells involved in NAFLD and NASH are known to have immunoregulatory properties and their imbalance will completely change the cytokine profile and form a pro-inflammatory microenvironment. It is necessary to fully answer the question of what initiators and metabolic imbalances are particularly important, considering sterile inflammation as the architect of the disease. Due to the shortage of elucidation of NASH progression, we discuss in this review, how inflammation is a key part of this development and we presume the targets should lead to inflammation and oxidative stress treatment.

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.

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.

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.

Anti-infectious and Anti-tumor Activities of ß-glucans.

BACKGROUND/AIM: The aim of this study was to directly compare the anti-infectious and anti-cancer effects of five commercially available glucans. MATERIALS AND METHODS: We used five different glucans isolated from algae, yeast, bacteria, oat, and mushroom. We compared their effects on the stimulation of phagocytosis of blood cells, on the secretion of IL-2, and on the inhibition of melanoma and breast and lung cancers. In addition, we evaluated the effects of glucan supplementation on two experimental models of infection. RESULTS: Most of the tested glucans stimulated phagocytosis and IL-2 secretion, reduced cancer growth, and ameliorated some effects of experimental infections. CONCLUSION: Glucans can produce significant pleiotropic effects, but the activity varies among individual samples.

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.

Endometrial cancer-is our knowledge changing?

In developed countries, endometrial cancer (EC) is the most frequent gynecologic malignancy in postmenopausal women. At the same time, EC has become one of the most common cancers in numerous developing countries, probably influenced by global epidemic of obesity. The majority of patients have low-grade endometrioid cancer with a high 5-year survival rate, but with high-risk EC, the survival rates are still rather low. However, despite intensive research in last decades, our knowledge of the mechanisms, risk factors, diagnosis and treatment have not significantly improved. The standard treatment of all types of EC is still a traditional combination of surgery, irradiation and/or chemotherapy, despite the fact that each of these options is not without having some negative side effects. Despite the fact that on the molecular level, EC is relatively well-studied, but the efforts to transform these findings into either diagnosis or therapies of EC remain elusive. In addition, some research into risk factors involved in the development or progression of EC seems to be more a fishing expedition than a well thought-out approach. The purpose of this review is to summarize the most recent developments in the search for biomarkers and prognostic markers and to discuss the progress in EC treatment.

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.

Immunomodulating Effects Exerted by Glucans Extracted from the King Oyster Culinary-Medicinal Mushroom Pleurotus eryngii (Agaricomycetes) Grown in Substrates Containing Various Concentrations of Olive Mill Waste.

We have recently demonstrated that we could enhance glucan content in Pleurotus eryngii following cultivation of the mushrooms on a substrate containing different concentrations of olive mill solid waste (OMSW). These changes are directly related to the content of OMSW in the growing substrate. Using dextran sulfate sodium (DSS)-in-flammatory bowel disease (IBD) mice model, we measured the colonic inflammatory response to the different glucan preparations. We found that the histology damaging score (HDS) resulting from DSS treatment reach a value of 11.8 ± 2.3 were efficiently downregulated by treatment with the fungal extracted glucans. Glucans extracted from stalks cultivated at 20% OMSW downregulated to a HDS value of 6.4 ± 0.5 whereas those cultivated at 80% OMSW showed the strongest effects (5.5 ± 0.6). Similar downregulatory effects were obtained for expression of various intestinal cytokines. All tested glucans were equally effective in regulating the number of CD14/CD16 monocytes from 18.2 ± 2.7% for DSS to 6.4 ± 2.0 for DSS + glucans extracted from stalks cultivated at 50% OMSW. We tested the effect of glucans on lipopolysaccharide-induced production of TNF-α, which demonstrated that stalk-derived glucans were more effective than caps-derived glucans. Isolated glucans competed with anti-Dectin-1 and anti-CR3 antibodies, indicating that they contain ß-glucans recognized by these receptors. In conclusion, the most effective glucans in ameliorating IBD-associated symptoms induced by DSS treatment in mice were glucan extracts prepared from the stalk of P. eryngii grown at higher concentrations of OMSW. We conclude that these stress-induced growing conditions may be helpful in selecting more effective glucans derived from edible mushrooms.

Glucans as New Anticancer Agents.

For decades, glucans have been studied for their biological and immunological activities. The scientific community has mainly focused on immune reactions, but other areas, such as cholesterol levels and diabetic retinopathy, have shown the positive effects of glucan supplementation. However, the majority of studies focused on possible cancer suppression, where glucans showed clear and significant effects on numerous types of cancers, leading not only to clinical trials, but to approval as an official drug. The aim of this review is to describe the current knowledge of this field.