Searching for a relationship between the elemental composition of archaeological bones and the occurrence of caries.

BACKGROUND: Although the macroscopic assessment of dental caries and the assessment of bone elemental composition are quite different, efforts can be made to identify commonalities in the assessment of health and nutritional quality. Both indicators are correlated with dietary habits and are dependent on taphonomic processes occurring in the postmortem substrate. However, teeth exhibit structural resilience of their hard tissues to adverse environmental factors. OBJECTIVES: The aim of the study was to establish a correlation between the elemental composition of bones and the presence of carious lesions. MATERIAL AND METHODS: The study material consisted of the following skeletal parts: 161 permanent teeth from 36 individuals and bridge fragments of 36 ribs. The presence of caries was assessed visually using a modified International Caries Detection & Assessment System (ICDAS II) scale. The rib samples were subjected to elemental analysis (zinc (Zn), iron (Fe), magnesium (Mg), calcium (Ca), phosphorus (P), strontium (Sr), barium (Ba)) using spectroscopic methods. RESULTS: The odontological and chemical analyses did not reveal any statistically significant relationships between the Ca/P diagenesis index and dental features. Postmortem tooth loss showed a weak correlation with the diagenesis index. CONCLUSIONS: Discoloration, cracks and flaking of the dental crown surfaces may be associated with the intensity of Ca/P diagenesis. However, no significant correlation was found between these phenomena. Among other elements, only Zn levels exhibited a correlation with the caries index.

Pulsed electric field induces exocytosis and overexpression of MAGE antigens in melanoma.

Nanosecond pulsed electric field (nsPEF) has emerged as a promising approach for inducing cell death in melanoma, either as a standalone treatment or in combination with chemotherapeutics. However, to date, there has been a shortage of studies exploring the impact of nsPEF on the expression of cancer-specific molecules. In this investigation, we sought to assess the effects of nsPEF on melanoma-specific MAGE (Melanoma Antigen Gene Protein Family) expression. To achieve this, melanoma cells were exposed to nsPEF with parameters set at 8 kV/cm, 200 ns duration, 100 pulses, and a frequency of 10 kHz. We also aimed to comprehensively describe the consequences of this electric field on melanoma cells' invasion and proliferation potential. Our findings reveal that following exposure to nsPEF, melanoma cells release microvesicles containing MAGE antigens, leading to a simultaneous increase in the expression and mRNA content of membrane-associated antigens such as MAGE-A1. Notably, we observed an unexpected increase in the expression of PD-1 as well. While we did not observe significant differences in the cells' proliferation or invasion potential, a remarkable alteration in the cells' metabolomic and lipidomic profiles towards a less aggressive phenotype was evident. Furthermore, we validated these results using ex vivo tissue cultures and 3D melanoma culture models. Our study demonstrates that nsPEF can elevate the expression of membrane-associated proteins, including melanoma-specific antigens. The mechanism underlying the overexpression of MAGE antigens involves the initial release of microvesicles containing MAGE antigens, followed by a gradual increase in mRNA levels, ultimately resulting in elevated expression of MAGE antigens post-experiment. These findings shed light on a novel method for modulating cancer cells to overexpress cancer-specific molecules, thereby potentially enhancing their sensitivity to targeted anticancer therapy.

Vitrification of feline ovarian tissue: Comparison of protocols based on equilibration time and temperature.

Global contraction of biodiversity pushed most members of Felidae into threatened or endangered list except the domestic cat (Felis catus) thence preferred as the best model for conservation studies. One of the emerging conservation strategies is vitrification of ovarian tissue which is field-friendly but not yet standardized. Thus, our main goal was to establish a suitable vitrification protocol for feline ovarian tissue in field condition. Feline ovarian tissue fragments were punched with biopsy punch (1.5 mm diameter) and divided into 4 groups. Group 1 was fresh control (Fr), while the other three were exposed to 3 vitrification protocols (VIT_CT, VIT_RT1 and VIT_RT2). VIT_CT involved two step equilibrations in solutions containing dimethyl sulfoxide (DMSO) and ethylene glycol (EG) for 10 min each at 4 °C. VIT_RT1 involved three step equilibration in solutions containing DMSO, EG, polyvinylpyrrolidone and sucrose for 14 min in total at room temperature, while in VIT_RT2 all conditions remained the same as in VIT_RT1 except equilibration timing which was reduced by half. After vitrification and warming, fragments were morphologically evaluated and then cultured for six days. Subsequently, follicular morphology, cellular proliferation (expression of Ki-67, MCM-7) and apoptosis (expression of caspase-3) were evaluated, and data obtained were analysed using generalised linear mixed model and chi square tests. Proportions of intact follicles were higher in Fr (P = 0.0001) and VIT_RT2 (P = 0.0383) in comparison to the other protocols both post warming and after the six-day culture. Generally, most follicles remained at primordial state which was confirmed by the low expression of Ki-67, MCM-7 markers. In conclusion, VIT_RT2 protocol, which has lower equilibration time at room temperature has proven superior thus recommended for vitrification of feline ovarian tissue.

New Equations for the Estimation of the Age of the Formation of the Harris Lines.

Harris Lines (HLs) are transverse, sclerotic lines that can be visualized by X-ray imaging and that occur in long bones, most commonly in the tibia and femur. HLs are associated with disrupted bone mineralization during endochondral ossification, affecting the normal growth process. The etiology of HLs is debated, with some claims linking their presence to detrimental factors such as inflammation, malnutrition, alcohol abuse, and diseases. The age at which HLs form can be estimated based on their location, which allows for a retrospective assessment of the individual's health status during childhood or youth. The current study is concerned with providing new equations to estimate the age of Harris Line occurrences using a simple calculating tool. Bone growth curves were derived based on a dataset provided by Byers in 1991 using non-linear estimation. The best model was chosen with the Akaike Information Criterion. New and old methods were compared through Bland-Altman plots. As a result, we managed to produce reliable, well-fitted growth curves, concordant with previous methods.

Chitin scaffolds derived from the marine demosponge Aplysina fistularis stimulate the differentiation of dental pulp stem cells.

The use of stem cells for tissue regeneration is a prominent trend in regenerative medicine and tissue engineering. In particular, dental pulp stem cells (DPSCs) have garnered considerable attention. When exposed to specific conditions, DPSCs have the ability to differentiate into osteoblasts and odontoblasts. Scaffolds are critical for cell differentiation because they replicate the 3D microenvironment of the niche and enhance cell adhesion, migration, and differentiation. The purpose of this study is to present the biological responses of human DPSCs to a purified 3D chitin scaffold derived from the marine demosponge Aplysina fistularis and modified with hydroxyapatite (HAp). Responses examined included proliferation, adhesion, and differentiation. The control culture consisted of the human osteoblast cell line, hFOB 1.19. Electron microscopy was used to examine the ultrastructure of the cells (transmission electron microscopy) and the surface of the scaffold (scanning electron microscopy). Cell adhesion to the scaffolds was determined by neutral red and crystal violet staining methods. An alkaline phosphatase (ALP) assay was used for assessing osteoblast/odontoblast differentiation. We evaluated the expression of osteogenic marker genes by performing ddPCR for ALP, RUNX2, and SPP1 mRNA expression levels. The results show that the chitin biomaterial provides a favorable environment for DPSC and hFOB 1.19 cell adhesion and supports both cell proliferation and differentiation. The chitin scaffold, especially with HAp modification, isolated from A. fistularis can make a significant contribution to tissue engineering and regenerative medicine.

Histological analysis of forearm superficial veins structure.

BACKGROUND: The connection between the basilic and cephalic veins of the forearm shows considerable interindividual variation. Depending on its form, the most common types of venous connections are M-, N- or Y-shaped. This study aims to compare the metric traits of the basilic and cephalic veins and the relative content of smooth muscle/collagen fibers/elastic fibers in their walls and to determine the differences between the forearm venous systems. MATERIALS AND METHODS: The study was performed on 42 veins collected from 26 deceased individuals between the ages of 19 and 50 years. Vein sections were fixed, embedded in paraffin blocks and used to prepare histological slides, stained according to pentachrome Movat's method. Venous metrics were assessed and the percentage of muscle, elastic and collagen fibers was determined using the Trainable Weka segmentation. Statistical analysis compared the M-type vein with the Y- and N-types, which were combined into one category. RESULTS AND CONCLUSIONS: Analysis showed a greater tunica media thickness in the M-type vein, with a greater lumen circumference in the Y/N types. Correlation analysis showed a correlation of vein metrics with elastic fibre content and a weak inverse correlation with the tunica media thickness. It can be hypothesized that the increased performance of N- and Y-types may be related to elastic fibers content.

Ultrastructural changes in feline oocytes during ovary storage for 24- and 48-hours.

Despite established microscopic markers of feline oocyte quality, little is known about their ultrastructural traits. To the best of our knowledge, there is no published report analysing the effect of 24 and 48 h ovarian storage time on the domestic cat oocytes characteristics at the ultrastructural level. Oocytes (n = 30) were classified using the light microscopy as good or bad quality and then proceeded for TEM observations. The location, shape, size and distribution of each organelle was noted in each examined oocyte. In in good quality oocytes the cytoplasmic organelles were generally easier to identify, and furthermore its distribution pattern was more obvious to spot than in bad quality ones. Whereas bad quality oocytes were typically characterised by the lower visibility of the cellular structures and cytoplasmic architecture was less apparent and often arranged without a predictable pattern. In good quality oocytes obtained from fresh ovaries cytoplasmic vacuoles (CVs) occupied a significantly larger area (0,72 vs. 0.18 CVs/µm2, respectively) than in bad quality ones, whereas in bad quality and stored oocytes more cytoplasm was occupied by lipid droplets (LDs) than in fresh good oocytes (0,22 ± 0,09 vs. 0,09 ± 0,05 respectively). It can be concluded that ultrastructure changes in feline oocytes during 24 and 48 h ovarian storage cannot be assessed in light microscopy. The ultrastructure of oocytes was seriously disturbed after 48 h of ovary storage, despite being classified as good quality. However, further investigations utilizing more cells are necessary to confirm reported traits of ultrastructure changes in stored and non-stored oocytes of good and bad quality.

Quantitative Phase Imaging Detecting the Hypoxia-Induced Patterns in Healthy and Neoplastic Human Colonic Epithelial Cells.

Hypoxia is a frequent phenomenon during carcinogenesis and may lead to functional and structural changes in proliferating cancer cells. Colorectal cancer (CRC) is one of the most common neoplasms in which hypoxia is associated with progression. The aim of this study was to assess the optical parameters and microanatomy of CRC and the normal intestinal epithelium cells using the digital holotomography (DHT) method. The examination was conducted on cancer (HT-29, LoVo) and normal colonic cells (CCD-18Co) cultured in normoxic and hypoxic environments. The assessment included optical parameters such as the refractive index (RI) and dry mass as well as the morphological features. Hypoxia decreased the RI in all cells as well as in their cytoplasm, nucleus, and nucleoli. The opposite tendency was noted for spheroid-vesicular structures, where the RI was higher for the hypoxic state. The total volume of hypoxic CCD-18Co and LoVo cells was decreased, while an increase in this parameter was observed for HT-29 cells. Hypoxia increased the radius and cell volume, including the dry mass of the vesicular content. The changes in the optics and morphology of hypoxic cells may suggest the possibility of using DHT in the detection of circulating tumor cells (CTCs).

Morphology of the antegonial notch and its utility in the determination of sex on skeletal materials.

A number of criteria for the assessment of biological sex, which are applied to living or recently deceased individuals, have been developed, such as genetic, chromosomal, gonadal, hormonal, and phenotypic criteria. Features of a metric and descriptive nature are used to assess the sex of skeletal materials. The diagnostic features of the skull are concentrated in the craniofacial region and around the eye sockets. The mandible is a diagnostically important part of the skull, on which a complex of features is visible. These features develop up to the third decade of life. The goal of the research was to assess the suitability of the parameters of the preangular notch, in other words, the length, height, and surface area for sex prediction applied to skeletal materials. The study included computed tomography images of the masticatory system of 194 patients, consisting of 83 females and 111 males, aged from 16 to 93 years. The three straight lines which correspond to the sides of the triangle representing the notch, in addition to its height, were determined and measured digitally. The receiver operating characteristic method was used to assess the usefulness of the studied features for the purposes of sex prediction. The sensitivity of the test ranged from 51.4% to 67% for the parameters of the preangular notch on the right-hand side, and from 44.4% to 80.2% on the left-hand side. The most reliable predictive models were obtained for two features (shown in the graphical abstract). However, when taking into account, the specificity and sensitivity of the tests presented here, only the length of side AB (a basal length of the notch) can be regarded as a feature that supports the assessment of sex on the basis of other diagnostic features of the mandible. The size and shape of the preangular notch should be treated as auxiliary features in the assessment of sex. For this reason, it is recommended that they should be applied simultaneously to the set of features described in the section on anthropological standards.

Identifying the Molecular Mechanisms and Types of Cell Death Induced by bio- and pyr-Silica Nanoparticles in Endothelial Cells.

The term "nanosilica" refers to materials containing ultrafine particles. They have gained a rapid increase in popularity in a variety of applications and in numerous aspects of human life. Due to their unique physicochemical properties, SiO2 nanoparticles have attracted significant attention in the field of biomedicine. This study aimed to elucidate the mechanism underlying the cellular response to stress which is induced by the exposure of cells to both biogenic and pyrogenic silica nanoparticles and which may lead to their death. Both TEM and fluorescence microscopy investigations confirmed molecular changes in cells after treatment with silica nanoparticles. The cytotoxic activity of the compounds and intracellular RNS were determined in relation to HMEC-1 cells using the fluorimetric method. Apoptosis was quantified by microscopic assessment and by flow cytometry. Furthermore, the impact of nanosilica on cell migration and cell cycle arrest were determined. The obtained results compared the biological effects of mesoporous silica nanoparticles extracted from Urtica dioica L. and pyrogenic material and indicated that both types of NPs have an impact on RNS production causing apoptosis, necrosis, and autophagy. Although mesoporous silica nanoparticles did not cause cell cycle arrest, at the concentration of 50 µg/mL and higher they could disturb redox balance and stimulate cell migration.

Nutritional reconstruction in an early modern population: Searching for a relationship between dental microwear and bone element composition.

BACKGROUND: Observing the microwear patterns of the dental crowns enamel surface can provide information on the ingredients and structure of the food consumed, but also on eating habits and lifestyle. Major role in reconstructing the diet and lifestyle of past populations is played by the analysis of alkaline earth metals, such as strontium, barium, zinc and calcium. Ba and Sr are indicators of the consumption of vegetables, plants (cereals and legumes) and marine organisms. This study aims to assess dietary diversity and identify its components based on microscopic techniques and chemical analyses of material from early modern archaeological sites in Wroclaw, Poland. METHODS: The material consisted of 36 permanent molars and the intrasternal parts of 122 first ribs, collected from 6 Wroclaw early modern cemeteries. Tooth microwear was evaluated on Scanning electron microscopy images, with Microwear 4.02 software. Bone chemical composition (Ca, P, Ba, Sr content) was evaluated with mass spectrometry. RESULTS: Most lines were present on the teeth from St. Mary Magdalene Cemetery, with the lowest average number of lines observed on the teeth from St. Barbara Cemetery. The Ca/P ratios calculated for different sites formed two clusters that allows to distinguish two groups of archaeological sites with different bone preservation status. Number of differences in Ba/Sr, Sr/Ca, Ba/Ca ratios was found between disctinct archaeological sites. A number of correlations were found between the concentration of the chemical elements, but no statistically significant correlation was found between the microwear characteristics and the proportion of the elements studied. Some strong correlations were found between microwear features and the Ca/P ratio. CONCLUSIONS: the different values of Sr/Ca, Ba/Ca and Ba/Sr ratios indicate different diets in the different communities. The data obtained indicate a mixed diet, with a relatively high proportion of animal products throughout Wroclaw. Conclusions should be treated with caution due to secondary diagenesis. The lack of interdependence between microwear and chemical composition characteristics suggests that the two methods should be considered complementary and not overlapping, as they provide different insights into the diets of past populations. The comparison of microwear between different sites should always take into account secondary diagenesis and the burial environment, as these influence the characteristics of microwear.

Cardiovascular Risk and Endothelial Dysfunction in Primary Sjogren Syndrome Is Related to the Disease Activity.

The aim of our study was to evaluate if endothelial-dysfunction (ED) occurs in patients with primary Sjogren syndrome (pSS) and whether it is associated with the disease characteristics and activity. A total of 46 patients with pSS and 30 controls, without known cardiovascular disease, were enrolled in this study. A flow-mediated-dilation (FMD) of the brachial artery, plasma concentrations of the nitric oxide (NO) metabolic pathway (ADMA, L-arginine, SDMA, cGMP), and markers of endothelial inflammatory function (PAI-1, sE-selectin) and angiogenesis (angiostatin, VEGF) were analyzed. The FMD was significantly lower in pSS patients (7.56 ± 3.08 vs. 10.91 ± 1.02%, p = 0.043) and positively correlated with the Ro/SS-A-antibodies (r = 0.34, p = 0.03), pulmonary involvement (r = 0.52, p = 0.001) and inversely with ADMA (r = -0.35, p = 0.04). Plasma ADMA, L-arginine and angiostatin levels were significantly higher in pSS patients (0.39 ± 0.08 vs. 0.36 ± 0.06 µmol/L, p = 0.05; 29.07 ± 6.7 vs. 25.4 ± 5.23 µmol/L, p = 0.01; 152.25 ± 60.99 vs. 120.07 ± 38.7 pg/mL, p = 0.0, respectively). ADMA was associated with ESSDAI (r = 0.33, p = 0.02), SCORE (r = 0.57, p = 0.00003) and focus score (r = 0.38, p = 0.04). In the multiple regression analysis, the ESSDAI was significantly and independently associated with plasma ADMA levels (ß = 0.24, p = 0.04). Moreover, plasma cGMP concentrations were negatively correlated with the disease duration (r = -0.31, p = 0.03). Endothelial function is impaired in patients with pSS and associated with the measures of disease activity, which supports the key-role of inflammation in developing and maintaining accelerated atherosclerosis.

Estimation of age at onset of linear enamel hypoplasia. New calculation tool, description and comparison of current methods.

Enamel Hypoplasia (EH) is known to be a useful indicator for wide range of detrimental factors in early childhood in past populations, such as nutritional disturbances, mechanical trauma, disease, metabolic, and/or genetic disorders. EH may be divided into three categories: pits, grooves, and lines, where the last two are referred to as "Linear Enamel Hypoplasia" (LEH). The regularity of enamel formation allows retrospective determination of the age of LEH formation. The current article reviews and compares the best-known methods used to estimate age at LEH formation and provides a new computational tool. Growth curves for canines and incisors were developed based on tooth growth tables by previous authors. Optimal models were selected using the Akaike Information Criterion. A Microsoft Excel spreadsheet was created to calculate age at LEH formation using the most common methods. All method results were compared with an archaeological sample (44 teeth of 18 individuals from an early modern cemetery from Wroclaw, Poland) and a theoretical model. The results of the methods were compared pairwise with Bland-Altman plots. The current article provides a quick and easy-to-use tool for analyzing LEH chronology and comparing the results of different methods. As shown by the Bland-Altman plots, most methods provide approximately consistent results for LEHs formed at around 2-3 years of age. However, LEHs formed particularly early or late are more prone to discrepancies between different methods. Comparison of the age at LEH formation obtained by different methods should be done carefully - and the new LEH calculation tool with optimized equations provided in this publication can facilitate this process.

Antlerogenic stem cells extract accelerate chronic wound healing: a preliminary study.

BACKGROUND: Chronic wounds constitute a significant medical and social problem. Chronic wound treatment may be supported by various techniques, such as negative pressure therapy, phototherapy or stem cells therapy, yet most of those supporting therapies need more evidence to be used for standard wound care. Current study covers the use of sonicated Antlerogenic Stem Cells (ASC) extract on chronic wounds. METHODS: Study was performed on 20 dermatological patients with venous leg ulcers, divided into two groups - treated with and without ASC extract respectively. The area and circumference of the wounds during the follow-up visits were measured on the wound imprint. Dynamics of wound healing was determined and compared between control and study group; statistics includes changes in absolute values (wound area, circumference), as well as relative (percentage of wound decrease, circumference/area ratio) and their change in time. For the purpose of Ki-67 immunohistochemical staining, sections were sampled from the wound edge at distinct check-points during therapy. Results of both groups were compared with Student test or Mann-Whitney test, depending on results distribution. RESULTS: Besides Ki-67 expression, all tested wound healing parameters (including relative and absolute wound decrease and changes in circumference/area ratio) were statistically significant more favorable in experimental group. CONCLUSION: ASC extract significantly supported standard chronic wound treatment. Due to small population of study the results should be considered preliminary, yet promising for further research.

Assessing weaning stress - Relations between enamel hypoplasia, δ18O and δ13C values in human teeth obtained from early modern cemeteries in Wroclaw, Poland.

OBJECTIVES: The aim of this paper is to assess linear enamel hypoplasia (LEH) on canines of adults from early modern Wroclaw cemeteries to compare δ13C and δ18O values in enamel formed before, during and after LEH formation, and to attempt to find a link between the selected indicators of the weaning process. MATERIAL AND METHODS: 15 permanent canines with visible LEH were selected for analysis. Age at LEH formation was estimated using the Reid and Dean method. The perikymata count was used to estimate the duration of LEH formation. Incremental stable oxygen and carbon isotopes analysis was performed on tooth enamel to infer stress related to weaning and dietary patterns. Kruskal-Wallis ANOVA, Mann-Whitney U test and Spearman correlation were used in statistical inference. RESULTS: The average age of LEH formation was 3.14 years, with an average duration of 111 days. Stable carbon isotope values consistently increase in 73% of the individuals sampled. The values of δ18O do not show a dominant pattern. The average value of δ13C increases over the time of enamel formation. The δ13C values collected below LEH were negatively correlated with δ18O values and the duration of LEH termination. CONCLUSIONS: Marking of carbon and oxygen isotopes indicates different stages of weaning. Advancements in diet change (determined by higher δ13C) corresponds with faster recovery after physiological stress episode. There is no evidence for different breastfeeding models between distinct parishes in early modern Wroclaw.

Diagnodent and VistaCam may be unsuitable for the evaluation of dental caries in archeological teeth.

OBJECTIVES: The aim of the study was to compare the usefulness of fluorescence-based caries detection systems (Diagnodent and VistaCam) for the assessment of carious lesions on archeological molars. MATERIALS AND METHODS: The study material consisted of teeth from the Cemetery of St. Mary Magdalene (Cmentarz sw. Marii Magdaleny) in Wroclaw, Poland. A sample of 178 permanent molars from 38 skulls were examined. Five surfaces of teeth (occlusal, mesial, distal, buccal, and lingual) were assessed on either basically cleaned or sandblasted teeth. Six diagnostic methods were used to detect carious lesions: the visual classification of the International Caries Detection and Assessment System (ICDAS II), fluorescent methods (Diagnodent and VistaCam), X-ray, cone beam computed tomography and histological sections. The sensitivity and specificity of the methods were determined using receiver operating characteristic (ROC) curves and the correlation between the severity of dental caries and the readouts obtained with each method. RESULTS: In most cases, Diagnodent and VistaCam yielded unsatisfactory specificity and sensitivity values. The area under curve (AUC) values in ROC curves for Diagnodent and Vistacam were lower than the AUC values obtained for the ICDAS II visual classification. CONCLUSIONS: According to our results, in the case of archeological teeth, neither Diagnodent nor VistaCam can be regarded as a better diagnostic method than the ICDAS II visual classification of caries.

A Case of Syphilis with High Bone Arsenic Concentration from Early Modern Cemetery (Wroclaw, Poland).

Venereal syphilis is a sexually transmitted disease caused by Treponema pallidum - Gram-negative, slowly growing bacteria. The spread of the disease in the Old World was due to increased birth rate, urban population growth, migration and lack of knowledge concerning the epidemiology. In the past, the treatment was mainly symptomatic and included application of mercury compounds. The goal of the study was to present the case of advanced venereal syphilis found in early modern (16th-18thc) graveyard localized in Wroclaw, Poland. The object of the study is a cranium of a male whose age at death has been estimated to be over 55. In order to observe the morphological and paleopathological characteristics of the examined material, anthropometrics, computed tomography, spectrometry and microscopic methods were incorporated. Microscopic analysis revealed the presence of the extensive inflammatory lesions. Analyses indicate tertiary stage of venereal syphilis as the most probable cause of the observed lesions. Concentration of arsenic (16.17±0.58 µg/g) in examined bone samples was about hundred times bigger than average arsenic concentration in bones reported in other studies. Advanced stage of observed lesions along with high arsenic level may suggest long-lasting palliative care and usage of arsenic compound in therapeutic treatment of this chronic disease.

The expression of IL10RA in colorectal cancer and its correlation with the proliferation index and the clinical stage of the disease.

INTRODUCTION: Despite the widely described role of IL10 in immune response regulation during carcinogenesis, there is no established model describing the role of its receptor. The aim of this study is to elucidate the relationship between the subunit alpha of IL10 receptor (IL10RA) in the pathogenesis of colorectal cancer (CRC). METHODS: The study was conducted on archived paraffin blocks of 125 CRC patients, from which tissue microarrays (TMA) were made. These were subsequently used for immunohistochemistry to assess the expression of IL10RA, IL10, phosphorylated STAT3 (pSTAT3) and the Ki67 proliferation index. The intensity of both reactions was assessed by independent researchers using two approaches: digital image analysis and the Remmele and Stegner score (IRS). To assess the possible correlations between the two investigated markers and the clinical stage of CRC, the Pearson correlation coefficient was calculated. The expression of aforementioned proteins was assessed in tumor samples, healthy surgical margins and healthy control samples, obtained from cadavers during autopsy from the Department of Forensic Medicine. Statistical analysis was conducted using Statistica ver. 13.05 software. RESULTS: The final analysis included 105 CRC patients with complete clinical and pathological data, for whom the expressions of IL10RA, IL10, pSTAT3 and Ki67 were assessed using two independent methods. There was a positive correlation between the IL10RA expression and Ki-67 proliferation index (R = 0.63, p < 0.001) and a negative correlation between the IL10RA expression and the clinical stage of CRC (R = -0.21, p = 0.022). IL10RA correlated positively with pSTAT3 and IL10 in neoplastic tissue and tumor margin (with p < 0.01 for all correlations). We also observed a significantly higher expression of IL10RA in healthy surgical margins when compared to the actual tumor (p = 0.023, the paired t-test). The expression of IL10 was significantly higher in tumors than in healthy intestinal endothelium from control group. CONCLUSIONS: The correlations between the expression of IL10RA and the proliferation index or the clinical stage of CRC seem to confirm the importance of IL10RA in the pathogenesis of CRC. The higher expression of IL10RA in healthy surgical margins than in the tumor itself may suggest that IL10RA plays a role in regulating immune response to the neoplasm.

Association Between Interleukin-10 Receptors and the CD45-Immunophenotype of Central Nervous System Tumors: A Preliminary Study.

BACKGROUND/AIM: One of the current hypotheses assumes that brain tumors exert an immunosuppressive influence on the surrounding cellular environment. Interleukin-10 (IL-10) is one of the immunosuppressive cytokines modifying the biological activity of cancer. The aim of this study was to assess the expression of IL10R in CD45+ cells within primary brain tumors and metastases and establish its association with tumor basic immunophenotype. PATIENTS AND METHODS: Tissue samples were obtained intraoperatively during surgeries of 32 patients suffering from meningiomas (n=9), gliomas (n=12) and metastatic tumors (n=11). Expression was assessed with flow cytometry and immunohistochemical reactions. RESULTS: Expression of IL10R subunits within the leukocyte population (CD45+ cells) was significantly higher in primary tumors than in metastases. CONCLUSION: To the best of our knowledge, this is the first study describing a correlation between the IL10R expression on leukocytes and histological types of brain tumors.

Clinical Phenotype of Depression Affects Interleukin-6 Synthesis.

Major depressive disorder (MDD) is not a single disease, but a number of various ailments that form one entity. Psychomotor retardation, anhedonia, sleep disorders, an increased suicide risk, and anxiety are the main symptoms that often define the clinical diagnosis of depression. Interleukin-6 (IL-6), as one of the proinflammatory cytokines, seems to be overexpressed during certain mental disorders, including MDD. Overexpression of IL-6 in depression is thought to be a factor associated with bad prognosis and worse disease course. IL-6 may directly affect brain functioning and production of neurotransmitters; moreover, its concentration is correlated with certain clinical symptoms within the wide range of depressive symptomatology. Furthermore, there is a strong correlation between IL-6 synthesis and psychosomatic functioning of the patient. This article discusses potential sources and significance of IL-6 in the pathogenesis of depression.